Roles of each angiotensin II producing enzymes of each of the angiotensin II-producing enzymes were reviewed based on experimental models. In vascular tissues, angiotensin II is potentially cleaved from angiotensin I by angiotensin converting enzyme (ACE) and chymase. It has been confirmed that vascular tissues of humans, monkeys, dogs and hamsters have a chymase-dependent angiotensin II-forming pathway. Much like other hypertensive models, hamster hypertensive models show high levels of vascular ACE activity, but not chymase activity. In hypertensive hamsters, administration of either an ACE inhibitor or an angiotensin II type 1 (AT₁) receptor antagonist resulted in similar reductions in blood pressure, suggesting that chymase is not involved in the maintenance of high blood pressure in this model. In monkeys fed a high-cholesterol diet, ACE activity was increased in the atherosclerotic lesions, and an ACE inhibitor and an AT₁ receptor antagonist prevented atherosclerosis to a similar degree, suggesting that ACE may be mainly involved in the development of atherosclerosis. After balloon injury in dog vessels, both ACE and chymase activities were locally increased about 3-fold in the injured arteries, and an AT₁ receptor antagonist was effective in preventing the intimal formation, but an ACE inhibitor was ineffective. In dog grafted veins, the activities of chymase were increased 15-fold, but those of ACE were increased only 2-fold, and the intimal formation was suppressed by either an AT₁ receptor antagonist or a chymase inhibitor. In the normal vascular tissues, ACE plays a crucial role for angiotensin II production, whereas chymase is stored in mast cells in an inactive form. Chymase acquires the ability to form angiotensin II following mast cells activation followed by mast cells activation by a strong stimulus such as occurs in catheter-injury or grafting. Together, these results indicate that chymase plays a major role in the vascular angiotensin II-generating system, particularly in cases of vascular injury. (Hypertens Res 2001; 24: 189-193)

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The purpose of this study was to elucidate the underlying mechanisms of blunted nocturnal blood pressure reduction in non-dipper hypertensive patients. We studied the diurnal variations in systemic hemodynamic indices and baroreflex sensitivity. In 45 subjects with essential hypertension (24 men; mean age, 49±1 years), intra-arterial pressure was monitored telemetrically. Non-dippers were defined as those with a nocturnal reduction of systolic blood pressure of less than 10% of daytime systolic blood pressure. Stroke volume was determined using Wesseling’s pulse contour method, calibrated with indocyanine green dilution. Baroreflex sensitivity was calculated as Δpulse interval/Δsystolic blood pressure on spontaneous variations. The mean values of the hemodynamic parameters were calculated every 30min. Twenty-six subjects were classified as non-dippers. Daytime blood pressure was not significantly different between dippers (149±4/87±3 mmHg) and non-dippers (147±3/82±2 mmHg), while the nighttime blood pressure was significantly reduced in dippers (131±3/77±2 mmHg) but not in non-dippers (145±3/80±2 mmHg). Nocturnal decreases in both cardiac index and stroke index were smaller in non-dippers (−12.0±1.2% and 1.5±1.0%) than in dippers (−17.5±1.4% and −2.2±1.1%). Baroreflex sensitivity significantly increased at nighttime both in dippers (6.5±0.6 to 8.0±0.7 ms/mmHg) and in non-dippers (5.1±0.3 to 6.4±0.4 ms/mmHg). Neither daytime nor nighttime baroreflex sensitivity was significantly different between the groups. We conclude that the hemodynamics of non-dipper essential hypertension are characterized by an inadequate nocturnal decrease in cardiac index and stroke index, suggestive of relative volume expansion or malsuppressed sympathetic activity. (Hypretens Res 2001; 24: 195-201)

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The present study profiled patients who control doses of antihypertensive drugs by themselves based on self-monitoring of their blood pressure (self-controllers). A total of 1, 028 consecutive outpatients who were taking antihypertensive drugs and who were attending the cardiovascular outpatient clinic of our institute responded to a questionnaire in 1998. They were asked how often they measured their blood pressure, how often they missed taking their medication, and whether or not they had a chance to adjust the doses of antihypertensive drugs by themselves based on self-monitored blood pressure. The frequency of self-controlling of antihypertensive drugs was also examined in 918 patients on antihypertensive drugs in 1997. In 1997, 23 of 918 patients (2.5%) were self-controllers, and 26 of 1, 028 patients (2.5%) were self-controllers in 1998. The frequency of home blood-pressure measurement was significantly greater in self-controllers than in the remaining patients (non self-controllers)(p<0.01). The prevalence of proteinuria was significantly less in the former than in the latter. Prior to the start of antihypertensive drugs, blood pressure was significantly lower for the self-controllers (154.4±3.8/96.4±1.4 mmHg) than for the non self-controllers (169.3±0.7/101.7±0.4 mmHg)(p<0.001). Clinically measured blood pressures did not differ significantly between the self-controllers and non self-controllers. Thus, about 2.5% of patients on antihypertensive drugs controlled their drug doses by themselves based on self-monitoring of their blood pressure. These patients were characterized by having a milder form of hypertension and by more frequent home blood-pressure measurement than non self-controllers. (Hypertens Res 2001; 24: 203-207)

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We investigated changes in blood pressure and blood variables, including plasma catecholamines, serum glucose and insulin concentrations, during dental surgery. The study included 11 normotensive patients (age, 22.5±0.7 years) who underwent tooth extraction at Kyushu Dental College Hospital. Three to 7 days prior to dental surgery, blood pressure, pulse rate, and heart rate variability were measured every 30 min over 24 h. The low frequency (LF: 0.05 to 0.15 Hz) and high frequency (HF: 0.15 to 0.40 Hz) powers were calculated, and the ratio of LF to HF (LF/HF) and HF were used as indexes of sympathetic and parasympathetic activities, respectively. Lidocaine, 2% with epinephrine (1:80,000), was used as the local anesthetic for all patients. Systolic blood pressures significantly increased during dental surgery (+10.8±3.5 mmHg); however, this increase failed to correlate not only with baseline systolic blood pressure but with 24-h averaged blood pressures, LF/HF or HF. On the other hand, plasma epinephrine and norepinephrine concentrations increased during dental surgery, and peak values of these variables were obtained after local anesthesia and during tooth extraction, respectively. Serum glucose level increased after local anesthesia (control vs. Local anesthesia: 5.16±0.11 vs. 5.62±0.10 mmol/l; p<0.01); however, plasma insulin concentrations did not change significantly. These results suggest that 1) ambulatory measurements of blood pressure and heart rate variability over 24 h cannot predict the responses of blood pressure during dental surgery, and that 2) administration of local anesthetic and tooth extraction activate sympathoadrenal outflow, resulting in an increase in serum glucose level in normotensive subjects. (Hypertens Res 2001; 24: 209-214)

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Hypertension is one of the risk factors for the development of coronary artery disease as well as stroke. The National Nutrition Survey shows that the systolic and diastolic blood pressures of Japanese adults have decreased over time. These trends have plateaued during the last decade. We investigated national trends in blood pressure (BP) levels during these 10 years by plotting the relation between the mean BP levels during year t, BP(t), and those of the following year, BP(t+1). When we plotted the systolic BP levels of Japanese men and women aged 15 to 80 years, the trace revolved clockwise, with cycles of 4 to 5 years. The approximate center of the circular trace corresponding to data for 1985 through 1990 was at 134 mmHg in men and 129 mmHg in women, and the approximate center of a smaller circle was at 135 mmHg in men and 130 mmHg in women, respectively. In addition, with respect to the data for Japanese men in their 60s, the mean systolic BP level decreased linearly from 1982 to 1986, whereas it seemed to generate 4 circles after 1986. The approcimate center of the first circle was 146 mmHg in the men. The center of the second circle was 145 mmHg and that of the third circle was 144 mmHg. Plotting of the data for Japanese women of the same age group yielded the same number of circles as the data for men. Our method of documenting changes in the mean BP levels in Japanese adults provided information about a chaotic oscillation that occurred in the populations we studied. The centers of Lorenz-plotted circles may thus provide essential information about trends in the BP levels in these populations. (Hypertens Res 2001; 24: 215-219)

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Hemodialysis patients frequently show associated hypertension, which can lead to a number of cardiovascular complications. The aim of this study was to assess the effects of hypertension on the structure and function of the carotid artery and left ventricle (LV) in hemodialysis patients. In addition, we investigated the contribution of hemodialysis and other risk factors. Fifty-two hemodialysis patients, 71 hypertensive patients (HT group) and 30 normotensive subjects (NT group) were included in this study. Hemodialysis patients were divided into two groups: 35 patients with hypertension (HDHT group), and 17 patients without hypertension (HDNT group). We measured intima-media thickness (IMT), plaque score, end-diastolic diameter, and stiffness index β of the carotid artery by ultrasonography, and LV mass index (LVMi), endocardial fractional shortening (FS), and midwall FS (MWS) by echocardiography. A multiple stepwise regression analysis including hemodialysis, hypertension, diabetes mellitus, and other risk factors was also performed. IMT was significantly higher in the HT and HDHT groups than in the NT group. Plaque score and diameter of the carotid artery were higher in the HDHT group than in the other three groups. The stiffness index β was higher in the HDHT group than in the non-hemodialysis groups. In multivariate analysis, IMT was independently correlated with age and hypertension. Plaque score and stiffness index β were independently associated with age, hypertension, and hemodialysis. LVMi was higher in HT and hemodialysis-patients groups than in the NT group. Hypertension and hemodialysis were strong and independent predictors of LVMi. FS showed no significant differences among the four groups, but MWS was significantly lower among the hemodialysis patients than in the NT group. MWS was independently correlated with hemodialysis and diabetes. In conclusion, hemodialysis per se advanced both atherosclerosis and arteriosclerosis of the carotid artery. Moreover, it increased LVMi and caused cardiac dysfunction. Associated hypertension might thus accelerate the progression of atherosclerosis and arteriosclerosis of the carotid artery and the increase of LVMi. (Hypertens Res 2001; 24: 221-227)

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Peroxisome proliferator-activated receptor (PPAR)-γ ligands thiazolidinediones (TZDs) have recently been reported to be anti-hypertensive and anti-atherosclerotic. We have previously shown that one of the TZDs troglitazone significantly suppressed the transcription of both thromboxane receptor (TXR) and angiotensin II type 1 receptor (AT1R) genes in vascular smooth muscle cells (VSMCs) by activating PPAR-γ. In the persent study, we compared the effects of troglitazone and other TZDs on the transcription of these genes. TXR and AT1R mRNAs in rat VSMCs were determined by semi-quantitative RT-PCR. Luciferase chimeric constructs containing either the 989-bp rat TXR gene promoter or the 1, 969-bp rat AT1R gene promoter were transiently transfected into VSMCs. The cells were incubated with troglitazone, RS-1455 (a derivative of troglitazone which does not contain the hindered phenol resembling α-tocopherol), pioglitazone, or rosiglitazone for 12 h before harvesting. mRNA expression levels of TXR and AT1R were significantly decreased by troglitazone in contrast to rosiglitazone. TXR gene and AT1R gene transcription was significantly suppressed by troglitazone in a dose-dependent manner, while RS-1455 was less potent. Pioglitazone and rosiglitazone weakly suppressed the transcription of both genes in a manner almost similar to RS-1455. We have shown that troglitazone suppresses transcription of both the TXR and AT1R genes more potently than other TZDs. The structure of troglitazone and RS-1455 is identical except the hindered phenol, which is recently recognized to function as an antioxidant. Moreover, we have shown that the potency for activating PPAR-γ is almost identical between troglitazone and RS-1455. We therefore speculate that the strong transcriptional suppression of the TXR and AT1R genes by troglitazone may be mediated in part by its antioxidant effect. (Hypertens Res 2001; 24: 229-233)

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Trandolapril is the prodrug of an angiotensin-converting enzyme (ACE) inhibitor. It has been proposed that its active metabolite, trandolaprilat, is mainly excreted in bile, but this has not been clearly demonstrated. Recently it has been reported that temocaprilat, an active metabolite of the ACE inhibitor temocapril, is effectively excreted in bile via an ATP-dependent active transporter (canalicular multispecific organic anion transporter: cMOAT). To investigate whether trandolaprilat has the pharmacological ability to affect the cMOAT system in a manner similar to temocaprilat. The lipophilicity of trandolaprilat and temocaprilat was measured to determine the n-octanol-water partition coefficients. The dose-dependent inhibition of the uptake of [³H]-estradiol-17β-D-glucuronide and [³H]-2, 4-dinitrophenyl-S-glutathione, which are good substrates for cMOAT, in canalicular membrane vesicles (CMVs) prepared from Sprague-Dawley rats was determined in the presence of trandolaprilat and temocaprilat. The partition coefficient of trandolaprilat (log Po/w−1.1) was about 30 times higher than that of temocaprilat (log Po/w−2.5). The uptake of [³H]-estradiol-17β-D-glucuronide and [³H]-2, 4-dinitrophenyl-S-glutathione was dose-dependently inhibited by the presence of temocaprilat, but trandolaprilat had no effect on the transport of [³H]-estradiol-17β-D-glucuronide or [³H]-2, 4-dinitrophenyl-S-glutathione into CMVs even at concentrations as high as 200μM. It could be concluded that trandolaprilat has a higher lipophilicity than temocaprilat. But the hepatobiliary excretion system via cMOAT may not contribute to the excretion of trandolaprilat in bile. (Hypertens Res 2001; 24: 235-240)

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Endothelin and growth factors such as transforming growth factor (TGF)-β1 are important regulators of the cardiovascular system. Although increased production of endothelin-1 (ET-1) and TGF-β1 have been reported in left ventricular hypertrophy, the detailed roles of these substances in hypertrophy remain to be determined. To elucidate the cardioprotective effects of calcium antagonists in left ventricular hypertrophy, we evaluated the effects of long-term treatment with benidipine, a long-acting calcium antagonist, on preproET-1, ET_A receptor (ETAR) and TGF-β1 expression in the left ventricle and evaluated the relations between these effects and myocardial remodeling in Dahl salt-sensitive hypertensive (DS) rats fed a high-salt diet. After 5 weeks of feeding an 8% NaCl diet to 6-week-old DS rats (i.e., at 11 weeks of age), a distinct stage of concentric left ventricular hypertrophy (DSLVH) was noted. Benidipine (DSLVH-B group, n=8; 1 mg/kg/day, subdepressor dose) or vehicle (DSLVH-V group, n=8) was administered to 6-week-old DS rats for 5 weeks, or until the onset of DSLVH stage, and age-matched (11-week-old) Dahl salt-resistant rats fed the same diet served as a control group (DR-C, n=8). Blood pressure was similar between the DSLVH-B and DSLVH-V groups, but was significantly lower in DR-C rats. The preproET-1, ETAR and TGF-β1 expressions in the left ventricle were significantly higher in DSLVH-V than in DR-C rats, and significantly lower in DSLVH-B than in DSLVH-V. Benidipine administration resulted in significant improvements in the wall-to-lumen ratio and perivascular fibrosis in the coronary arterioles, and in myocardial fibrosis. We therefore concluded that myocardial remodeling and left ventricular hypertrophy in DS hypertensive rats fed a high-salt diet were significantly ameliorated by a subdepressor dose of benidipine, and that this amelioration was partly due to decreases in the expression of ET-1 and TGF-β1 in the left ventricle. (Hypertens Res 2001; 24: 241-250)

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Angiotensin II (Ang II) induces vascular smooth muscle cell (VSMC) hypertrophy, which results in several cardiovascular diseases. Ang II-induced cellular events have been mediated, in part, by reactive oxygen species (ROS) which also involve activation of mitogen-activated protein (MAP) kinases. Although it has been proposed that the therapeutic administration of antioxidants is useful for vascular diseases, the precise mechanisms which regulate ROS-sensitive signaling events have not been well characterized. Thus, we hypothesized that antioxidants may affect ROS-mediated MAP kinases activation induced by Ang II. The present findings showed that Ang II stimulated rapid and significant activation of ERK 1/2, JNK and p38 MAPK in cultured rat aortic smooth muscle cells (RASMC). Ang II-induced ERK 1/2 activation was not affected by all antioxidants examined, whereas JNK was sensitive to all antioxidants. In contrast, p38 MAPK activation was inhibited by DPI and ascorbic acid concentration-dependently, but by NAC only at high concentration. DETC and Trolox C had no effects on p38 MAPK activation by Ang II. We further examined the effects of antioxidants on Ang II-induced increases in oxygen consumption as an index of ROS generation in RASMC. DPI strongly inhibited Ang II-induced increases in oxygen consumption. DETC also inhibited Ang II-induced oxygen consumption, whereas ascorbic acid markedly augmented it. These findings suggest that the inhibitory effects of antioxidants on MAP kinases activation in VSMC are attributable, in part, to their modulating effects on ROS generation by Ang II in VSMC. Thus, inhibition of MAP kinases by antioxidants may imply their usefulness for relief of cardiovascular diseases. (Hypertens Res 2001; 24: 251-261)

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The present in vitro study was performed to investigate the effects of estriol (E3) on membrane fluidity of erythrocytes by means of an electron paramagnetic resonance (EPR) and spin-labeling method. E3 was shown to significantly decrease the order parameter (S) for 5-nitroxide stearate (5-NS) and the peak height ratio (h₀/h₋₁) for 16-NS obtained from EPR spectra of erythrocyte membranes. This finding indicated that E3 might increase the membrane fluidity of erythrocytes. The effect of E3 was significantly potentiated by the nitric oxide (NO) donor, S-nitroso-N-acetylpenicillamine (SNAP), and a cyclic guanosine 3',5'-monophosphate (cGMP) analog, 8-bromo-cGMP. In contrast, the change in the membrane fluidity induced by E3 was antagonized by the NO synthase inhibitor, L-N^G-nitroarginine-methyl-ester (L-NAME), and asymmetric dimethyl-L-arginine (ADMA). The results of the present study showed that E3 significantly increased the membrane fluidity and improved the microviscosity of erythrocyte membranes, partially mediated by an NO- and cGMP-dependent pathway. Furthermore, the data might be consistent with the hypothesis that E3 could have a beneficial effect on the rheological behavior of erythrocytes and may play a crucial role in the regulation of microcirculation. (Hypertens Res 2001; 24: 263-269)

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We examined the Ca²⁺-buffering function of the sarcoplasmic reticulum (SR) in the resting state of arteries from spontaneously hypertensive rats (SHR) at a prehypertensive stage. Differences in the effects of cyclopiazonic acid (CPA) and thapsigargin, agents that inhibit SR Ca²⁺-ATPase, and of ryanodine, which depletes SR Ca²⁺, on tension and cellular Ca²⁺ level were assessed in endothelium-denuded strips of femoral arteries from 4-week-old SHR and normotensive Wistar-Kyoto rats (WKY). Addition of CPA, thapsigargin or ryanodine to the resting state of the strips caused an elevation of cytosolic Ca²⁺ level and a contraction in both WKY and SHR. These responses were larger in SHR than in WKY. The contractions were inhibited strongly by 100 nM nifedipine or 3μM verapamil and were abolished by Ca²⁺-free solution. Nifedipine, verapamil or Ca²⁺-free solution itself caused a relaxation from the resting state of SHR strips, but not from that of WKY strips. The resting Ca²⁺ influx in arteries measured by a 5-min incubation with ⁴⁵Ca was significantly larger in SHR than in WKY. This influx was decreased by 10μM CPA or 10μM ryanodine in both WKY and SHR. These results suggest that in the resting state of the femoral artery from 4-week-old SHR, the greater part of the increased Ca²⁺ influx via L-type Ca²⁺ channels is buffered by Ca²⁺ uptake into the SR, while some Ca²⁺ reaches the myofilaments, resulting in the maintenance of resting tone. (Hypertens Res 2001; 24: 271-282)

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A 19-year-old man with moyamoya disease was diagnosed as having renovascular hypertension, based on stenosis of the proximal portion of the right renal artery with elevated plasma renin activity. Intravascular ultrasound (IVUS) imaging at the renal artery lesion revealed focal narrowing of the renal artery without vascular wall thickening (i.e., coarctation). The coarctation of the renal artery was adequately dilated by stent implantation after suboptimal balloon angioplasty. After the procedure, the patient’s hypertension improved. The findings of the present case suggest that IVUS-guided renal angioplasty is an effective therapeutic procedure for correcting coarctation of the renal artery in patients with moyamoya disease. (Hypertens Res 2001; 24: 283-287)

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Variants of atrial natriuretic peptide (ANP) are reported to be more common in blacks with hypertension than in normotensive controls and constitute an independent risk factor for cerebral infarction. The purpose of the present study was to investigate the role of ANP in the pathogenesis of essential hypertension (EH) in the Japanese. We investigated 2 previously reported ANP gene markers, G1837A and T2238C, for their possible associations with EH. A total of 233 individuals with EH and 213 age-matched normotensive (NT) control subjects were studied. The frequencies of the G and A alleles were 0.09 (42/466) and 0.91 (424/466), respectively, for the NT group and 0.11 (47/426) and 0.89 (379/426), respectively, for the EH group. These frequencies did not differ significantly between the two groups. The frequencies of the T and C alleles were 0.024 (11/466) and 0.97 (455/466), respectively, for the NT group and 0.03 (13/426) and 0.97 (413/426), respectively, for the EH group. These frequencies also did not differ significantly between the two groups. Neither G1837A nor the T2238C polymorphism of the ANP gene was associated with EH. Our findings do not support the hypothesis that the G1837A and T2238C polymorphisms of the ANP gene are markers for EH in the Japanese. (Hypertens Res 2001; 24: 291-294)

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Predisposition to essential hypertension is associated with gene polymorphisms of the renin angiotensin system (RAS). Gene polymorphisms of the angiotensinogen and angiotensin converting enzyme genes are known to be risk factors for hypertension, while few studies concerning the renin gene polymorphism have been published. In the present investigation, we carried out a case control study using a Japanese population to examine the genetic influence of the renin gene on the predisposition to hypertension. Patients (n=235) recruited from outpatients at Osaka University Hospital and diagnosed with essential hypertension or receiving long-term antihypertensive medication participated in the study. Normotensive control subjects (n=510) without a history of hypertension and without diabetes mellitus were recruited from the same population, and were sex-matched with experimental subjects. A polymorphism in intron 9 of the human renin gene was determined as the Mbo I restriction fragment length polymorphism (Mbo I-RFLP). There was no significant association between Mbo I-RFLP of the renin gene and predisposition to essential hypertension in Japanese (p>0.05, χ²=2.1). These results suggest that the Mbo I (+) allele of the renin gene does not increase the risk for hypertension in Japanese. (Hypertens Res 2001; 24: 295-298)

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The present study examined whether a genetic variant (−58T/C) in the promoter region of the human β₂ bradykinin receptor gene was genetically involved in essential hypertension. Chinese hypertensive subjects (n=120) and normotensive controls (n=98; sex- and age-matched with hypertensive) were recruited from the outpatients of Fu Wai hospital. Distribution of the −58T/C polymorphism was determined in patients and controls by means of PCR, SSCP, cloning and sequencing. The allelic frequencies were 0.56 for the C allele and 0.44 for the T allele in hypertensive subjects, and 0.46 for the C allele and 0.54 for the T allele in normotensive subjects. The allelic frequencies were in Hardy-Weinberg equilibrium. Significant differences between hypertensive and normotensive subjects were seen in the genotypes distribution (p=0.045) and allelic frequencies (p=0.033). These results suggested that −58C allele of the human β₂ bradykinin receptor gene may be an independent risk factor for essential hypertension in the Chinese Han population. (Hypertens Res 2001; 24: 299-302)

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The aim of this study was to determine the effect of Jiang-Tang-Ke-Li (JTKL), a Chinese medicine used to treat diabetes mellitus, on insulin resistance and hypertension in fructose-fed rats (FFR). Six-week-old male Sprague-Dawley rats were fed either normal rat chow (control) or a fructose-rich chow (FFR) for 6 weeks. For the last 2 weeks of the 6-week period of either diet, the rats were treated by gavage with gum arabic solution as a vehicle (control or FFR) or JTKL (3.24 g/kg/day; FFR+JT), and then an euglycemic hyperinsulinemic glucose clamp technique was performed to estimate insulin sensitivity. Systolic blood pressure was measured each week of the 6-week period. At the end of the glucose clamp, the soleus and extensor digitorum longus (EDL) muscles were dissected out for determination of the role of tumor necrosis factor (TNF)-α by an ELISA assay. Systolic blood pressures in the FFR groups were significantly higher than that in the control group, although there was no effect on systolic blood pressure for the last 2 weeks of treatment with JTKL. The average rate of glucose infusion during the glucose clamp, as an index of insulin sensitivity (M value), was significantly lower in the FFR than in the control rats, and treatment with JTKL for 2 weeks significantly increased the M value to that of control. TNF-α levels were significantly higher in the soleus and EDL muscles of the FFR (480±46 and 570±45 pg/g wet tissue in the soleus and EDL muscles, respectively) than in those of the control rats (177±34 and 206±33 pg/g wet tissue in the soleus and EDL muscles, respectively; p<0.01). Treatment with JTKL for 2 weeks significantly lowered TNF-α levels to the control levels (189±22 and 239±92 pg/g wet tissue in the soleus and EDL muscles, respectively). The results suggest that the Chinese medicine JTKL improves insulin resistance and modulates TNF-α in the soleus and EDL muscles in hypertensive and insulin-resistant fructose-fed rats. (Hypertens Res 2001; 24: 303-309)

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To evaluate the clinical efficacy of long-acting nitrates, isosorbide-5-mononitrate (IS-5-MN), on large artery distensibility in patients with essential hypertension. Large arterial distensibility was assessed by automatic noninvasive measurement of the carotid-femoral pulse wave velocity (PWV). Seventeen patients aged 62.53±7.94 years (mean±SD) with essential hypertension undering long-term antihypertensive therapy were studied in this trial. PWV was measured 2 weeks and 4 weeks after oral administration of IS-5-MN (30 mg once daily) with previous therapy. There was no significant difference in systolic blood pressure, diastolic blood pressure, pulse pressure or heart rate at 2 weeks and 4 weeks after treatment compared with baseline. The carotid-femoral PWV decreased significantly at 2 and 4 weeks after treatment (p<0.05, p<0.05, respectively). Long-acting nitrates have potential value in improving large arterial distensibility in patients with essential hypertension independent of blood pressure alteration. It might be used as an effectively additive drug in hypertension control. (Hypertens Res 2001; 24: 311-314)

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Our aim was to examine differences in dietary intake and blood pressure (BP) and their associations in four different ethnic Chinese populations, the Han, the Uygur, the Kazak and Tibetan subjects. This study used a sub-database of the Chinese sample of the WHO-Cardiovascular Diseases and Alimentary Comparison (CARDIAC) Study. The WHO-CARDIAC Study was a multicenter cross-sectional study. In each center, 100 men and 100 women aged 48-56 years were selected at random from the local population. Various markers of dietary intake and their relation with BP were studied. The results of the present study indicated the following. 1) There were significant differences in mean BP and prevalence rates of hypertension, with both being higher in the Kazak and Tibetan subjects than in Han and Uygur subjects. 2) The highest mean body mass index (BMI) was observed in the Kazak subjects, while the highest 24-h urinary sodium (Na) and sodium to potassium (Na/K) ratio excretion were observed in the Tibetan subjects. There were also significant differences in other factors, such as magnesium, 3-methylhistidine (3MH)(a biological marker of animal protein intake) and taurine (a biological marker of seafood intake) excretion levels among the four ethnic peoples. 3) In general, BMI, Na and/or Na/K ratios were positively, and 3MH/creatinine and taurine/creatinine ratios were negatively associated with BP. 4) After adjustment for age, sex and potassium, subjects with obesity (BMI≥26 kg/m²) had significantly higher relative risk of being hypertensive (HT) than those with BMI<26 kg/m² in the Han, Uygur and Kazak populations; and subjects with elevated sodium excretion (Na≥244 mmol/day) had significantly higher relative risk of being HT than those with Na<244 mmol/day in the Han, Uygur and Tibetan populations. In conclusion, mean BP and prevalence rates of hypertension were significantly different among the four ethnic groups. These differences are likely to be due, at least in part, to the differences in several diet-related factors, which in turn are associated with culture and environmental differences. Different health promotion strategies might thus be emphasized in different populations. (Hypertens Res 2001; 24: 315-322)

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Angiotensin II (Ang II) and apoptosis contribute significantly to myocardial ischemia-reperfusion (I-R) injury. Evidence indicates that Ang II may activate apoptosis in myocytes. The present study was undertaken to investigate the effects of angiotensin receptor blockers (ARBs), candesartan, on the apoptosis of cardiac myocytes in rats after I-R. Rats were divided into a control group, a candesartan group I (0.015 mg/kg), and a candesartan group II (0.03 mg/kg). Candesartan was intravenously administered 30 min before ischemia. All rats were subjected to 30 min of coronary occlusion followed by 3 h of reperfusion. The data showed that left ventricular (LV) systolic pressure and LV +dp/dt was decreased after administration of candesartan, but increased after reperfusion in the candesartan group II, compared with those in the candesartan group I and control group. LV −dp/dt was decreased after candesartan administration in candesartan group II. The number of apoptotic cells in the candesartan groups (497±204 and 543±254, respectively) was higher than that in the control group (287±166; p<0.05). There was no significant difference in infarct size among the three groups. However, plasma CPK was lower in the candesartan groups than in the control group. Northern blot analysis showed that p53 mRNA was upregulated in the candesartan groups, in association with increased expression of bax mRNA. Immunohistochemical analysis showed that p53 and bax immunoreactivity were increased in both of the candesartan groups. In conclusion, candesartan increased apoptosis in the rat hearts after acute I-R, and this increase was possibly mediated by upregulation of p53 and bax gene expressions. In addition, candesartan was shown to improve LV function, in association with reduction of CPK release. (Hypertens Res 2001; 24: 323-329)

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