To clarify the effects of nifedipine and enalapril on cardiac autonomic nervous function during postural changes, power spectral analysis of heart rate variability and humoral factors was performed during tilt tests before and after 3 months of drug administration. The study group consisted of 29 elderly patients with hypertension (mean age, 69 yr), who were divided into two groups: 15 patients received nifedipine (group N) and 14 received enalapril (group E). In group N, systolic blood pressure was significantly decreased and the percent changes in low-frequency coefficient of component variance, normalized low-frequency: high-frequency ratio, and plasma norepinephrine concentration were significantly altered by nifedipine administration. Group E, in contrast, showed no significant decrease in SBP, and only the percent change in high-frequency coefficient of component variance increased significantly after enalapril administration. These results suggest that cardiac autonomic nervous function is markedly impaired during the tilt test after long-term treatment with nifedipine, whereas it is well-maintained after long-term treatment with enalapril. (Hypertens Res 1997; 20: 1-6)

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We compared the effects of two long-term antihypertensive treatments (ACE inhibitors vs. Ca antagonists) on left ventricular hypertrophy (LVH) and LV function in patients with essential hypertension and LVH. After a washout period of at least 4wk, ceronapril or delapril was administered to 18 patients and nifedipine or nicardipine to 15 patients for 6 months. Mean blood pressure (MBP), LV mass (LVM), LV fractional shortening (FS), systolic time intervals (ejection time/pre-ejection period ratio= ET/PEP), and isovolumic relaxation time (IRT) were examined in the pretreatment phase and after 6 months of treatment. MBP and LVM significantly and similarly decreased after treatment in both groups (ACE inhibitors vs. Ca antagonists, ΔMBP: -17.1±1.3 vs. -16.9±1.6%; ΔLVM: -11.7 +2.7 vs. -10.0+3.8%, both p=not significant). ACE inhibitors produced significant beneficial changes in FS, ET/PEP, and IRT after treatment as compared with Ca antagonists (ACE inhibitors vs. Ca antagonists, ΔFS: 11.8±3.3 vs. 5.1±4.1%, p<0.05; ΔET/PEP: 11.9±2.3 vs. 4.7±6.4%, p< 0.05; ΔIRT: -12.0±3.4 vs. -3.8±6.1%, p<0.05). The results indicate that both ACE inhibitors and Ca antagonists induce significant and similar reductions in blood pressure and LVM in hypertensive patients. ACE inhibitors produce significant improvements in LV function in both systolic and diastolic phases as compared with Ca antagonists. (Hypertens Res 1997; 20: 7-10)

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Decreased arterial compliance (ACo) and increased arterial resistance are the major alterations of arterial function in patients with hypertension. The influence of decreased ACo on the heart was investigated in patients with hypertension. Patients with a systolic blood pressure of >140mmHg, a diastolic blood pressure of >90mmHg, or both, who had normal coronary arteriograms were enrolled. These patients were divided into two groups according to the value of ACo: Group I, patients with ACo_??_0.9 ml/mmHg (n=15); and Group II, patients with ACo<0.9ml/mmHg (n=13). There were no significant differences in arterial resistance, age, gender, and body surface area between the groups. Echocardiographic, hemodynamic, and exercise stress test variables were compared between the groups. There were no differences between the groups in left ventricular (LV) wall thickness and volume, cardiac output, LV end-diastolic pressure, and LV ejection fraction. However, pulse pressure was higher in Group II than in Group I. Ergometer exercise stress testing revealed that, although exercise duration and the peak rate-pressure product were similar in the two groups, ST segment depression of _??_1.0mm on the exercise electrocardiograms was induced more frequently in Group II than in Group I (92% vs. 27%, p <0.001). Thus, the decrease in ACo in patients with hypertension may not significantly affect LV wall thickness, volume, or ejection fraction; however, it may increase pulse pressure and may adversely affect coronary circulation, as suggested by the ST segment depression on exercise electrocardiograms. (Hypertens Res 1997; 20: 11-16)

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This study was conducted to investigate whether altered vascular responsiveness to vasoactive compounds contributes to the development of hypertension in diet-induced hyperinsulinemic rats. Male Sprague-Dawley rats were randomly assigned to receive high fructose, high sucrose, or standard rat chow for 13-18wk. Blood pressure was monitored by indirect (tail-cuff) measurements at regular intervals during the diet treatment. Vascular responses to various vasoactive agents were studied both in vivo and in vitro. Blood pressure response, as assessed by direct (intra-arterial) measurement, to graded dose infusions of norepinephrine or angiotensin II or bolus infusion of acetylcholine were determined. In vitro vascular responses of the tail arteries to exogenous norepinephrine were also studied. The fructose- and the sucrose-fed rats had significantly higher blood pressure than controls. Serum insulin levels were also significantly higher in fructose- and sucrose-fed rats than in controls. The blood pressure responses to graded infusions of norepinephrine were significantly less in the fructose-fed rats than in controls. The blood pressure responses to angiotensin II and acetylcholine infusion were not significantly different among the three groups of rats. In vitro studies of vascular reactivity in the tail arteries revealed than the concentration of norepinephrine that produced half-maximal contraction (NE EC₅₀) was significantly higher in the fructose group than control. Thus, impaired vascular responses to exogenous norepinephrine were observed in fructose-fed rats both in vivo and in vitro. This may be due to an adaptation to increased sympathetic nervous activity, or may be a compensatory response to other structural or functional changes that produce hypertension in this model. (Hypertens Res 1997; 20: 17-21)

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The effects of antihypertensive treatment on regression of left ventricular hypertrophy and on left ventricular systolic and diastolic function were investigated echocardiographically in 13 untreated patients with mild hypertension (group I) and 16 untreated patients with moderate to severe hypertension (group II). The left ventricular mass index, left ventricular wall thickness, end-systolic left ventricular wall stress, and diastolic filling indexes before treatment were significantly higher in group II than in group I (p<0.01). The blood pressure of both groups decreased significantly after antihypertensive treatment (mean duration of follow-up, 1.8±0.3 yr in group I and 2.0±0.4 yr in group II) (p<0.01). The left ventricular mass index did not change in group I, whereas it decreased significantly in group II (p< 0.01). The relation between fractional shortening and end-systolic wall stress was similar in both groups before treatment and was unaltered by treatment in either group. After treatment, peak velocity in early diastole (E) significantly increased in both groups; however, peak velocity in late diastole (A) did not decrease in either group. The A/E ratio was significantly decreased in both groups and was significantly higher in group II than in group I (p<0.01). In conclusion, the results suggest that intrinsic contractility may not be affected by left ventricular hypertrophy or regression of left ventricular hypertrophy. A/E ratio decreased after antihypertensive treatment in patients with mild hypertension mainly because of a decrease in blood pressure. (Hypertens Res 1997; 20: 23-28)

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We have previously reported that desmopressin (dDAVP) increased the lumen diameter of norepinephrine (NE)-constricted isolated microperfused rabbit afferent arterioles. In this study, we examined the role of nitric oxide in dDAVP-induced vasodilation of afferent arterioles. We microdissected a superficial afferent arteriole from the kidney of a New Zealand white rabbit. Each afferent arteriole was cannulated with a pipette system and microperfused in vitro at 60mmHg. dDAVP increased the lumen diameter of NE-preconstricted rabbit afferent arterioles dose-dependently. dDAVP-induced vasodilation was abolished by pretreatment with N^G-nitro-L-arginine (L-NNA, 10^-4M) (L-NNA+NE, 6.7±1.1μm; L-NNA+NE+dDAVP, 7.3±1.4μm, n=8). dDAVP increased the lumen diameter of NE-preconstricted afferent arterioles pretreated with L-NNA and L-arginine (10^-2M) (L-NNA+L-arginine+NE, 6.1± 1.1μm; L-NNA+L-arginine+NE+dDAVP, 8.7±0.9μm*; * p<0.05, n=6). Aspirin-DL-lysine (10^-4M) did not influence dDAVP-induced afferent arteriolar vasodilation (aspirin+NE, 6.4±0.8μm; aspirin+ NE+dDAVP, 9.6±1.3μm*; * p<0.05, n= 5). These results suggest that nitric oxide may be responsible for dDAVP-induced afferent arteriolar vasodilation. (Hypertens Res 1997; 20: 29-34)

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To test the hypothesis that endothelin (ET) and nitric oxide (NO) interact in modulating the sympathetic nervous system in conscious rats, as they do in the endothelium, mean arterial pressure (MAP), heart rate, and renal sympathetic nerve activity (RSNA) were recorded in Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) given losartan and compared before and during intravenous infusion of an NO synthase inhibitor, L-NMMA (0.25mg/kg/min). The slope of the relation between RSNA and MAP to blood pressure reduction was increased in the presence of L-NMMA (from 0.6±0.1 to 2.8± 0.2), suggesting that endogenous NO suppresses the reflex increase in RSNA. Since NO inhibits ET production in the endothelium, we speculated that the increase in MAP-RSNA slope was due partly to an unmasking of ET, and thus recorded MAP, heart rate, and RSNA during intravenous infusions of both L-NMMA and the ET-type-A-receptor antagonist BQ-485 (0.10mg/kg/min). The slope decreased significantly in SHR when BQ-485 was added (1.5±0.2), but not in WKY, implying that unmasked ET enhanced the sympathetic increase via ET_A receptors in hypertensive rats. An ET_B- receptor antagonist potentiated the sympathetic response only in WKY rats. These results suggest that NO suppressed the reflex increase in RSNA to blood pressure reduction, while ET uncovered by L-NMMA enhanced the sympatho-activation, indicating an interaction between ET and NO in modulating the sympathetic nervous system in conscious hypertensive animals in vivo. In contrast, the interaction was not observed in normotensive rats. (Hypertens Res 1997; 20: 35-42)

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Nitric oxide (NO) has been suggested to play important roles in the pathophysiology of various cardiovascular diseases. This study tested the hypothesis that an attenuated biological action of NO in hypertension is attributed to a change in the gene expression of NO synthase (NOS), a key enzyme involved in NO formation. The expression level of mRNA of endothelial type NOS (NOS-III) was determined in stroke-prone spontaneously hypertensive rats (SHR-SP/Izm) and Wistar Kyoto rats (WKY/Izm) by ribonuclease protection assay using a partial clone as probe. NOS-III mRNA was expressed ubiquitously in various tissues of WKY/Izm and SHR-SP/Izm either at 5wk or 13wk of age. There was no significant difference in the tissue expression of NOS-III mRNA between the two strains at either age. The intensity and localization of the hybridization signal for NOS-III mRNA in the heart of SHR-SP/Izm did not differ from those in the heart of WKY/Izm. These results suggest that the attenuated biological action of NO implied in genetically hypertensive rats is not attributed to an abnormality at the level of NOS-III mRNA expression in the tissues, although lack of an increase in NOS-III gene expression, despite the hypertensive hemodynamic stress, may modify the blood pressure in hypertension. (Hypertens Res 1997; 20: 43-49)

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Polyclonal antibodies have been prepared against synthetic peptides of human angiotensin II type-1 (AT₁) and type-2 (AT₂) receptors. Synthetic peptides corresponded to amino acids 15-24 of AT₁ receptor and amino acids 241-253 of AT₂ receptor. Western blot analysis of membranes from cell homogenates of COS-7 cells transfected with expression plasmids for mouse AT₁b receptor, human vascular smooth muscle cells, and rat peripheral tissue demonstrated a major band of MW 44, 000 with AT₁ receptor antibody. Cell homogenates of COS-7 cells transfected with expression plasmids for human AT₂ receptor showed a band of MW 44, 000 with AT₂ receptor antibody. Tissue homogenate of rat adrenal medulla and human pheochromocytoma presented a major band of MW 52, 000 and a minor band of MW 44, 000 with AT₂ receptor antibody. AT₁ receptor expression was in the following order: rat aorta _??_lung, kidney, spleen, adrenal cortex>adrenal medulla, heart. Expression of AT₂ receptor was in the following order: rat adrenal medulla>cortex, kidney, heart. Three-day treatment with CS866, an AT₁ receptor antagonist, and temocapril, an angiotensin-converting enzyme inhibitor, suppressed AT₁ receptor expression in the rat adrenal cortex, but not in the heart or adrenal medulla. AT₂ expression was not affected by treatment with these drugs. These results suggest that newly developed antibodies for AT₁ and AT₂ receptors are useful in elucidating the regulation of subtype-specific receptor expression, and that AT₁ but not AT₂ receptors in adrenal tissue are regulated by angiotensin II. (Hypertens Res 1997; 20: 51-55)

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To clarify the precise relationship between sodium and nitric oxide (NO), we studied the effects of altered sodium intake on NO production. Male Wistar rats were maintained on a low-sodium (0.2% NaCl), normal-sodium (2% NaCl), or high-sodium (8% NaCl) diet for 10 days or 8 weeks; 24-h urine was collected at those times for assay of nitrate ion (NO3_-), a stable metabolite of NO, and of cyclic GMP. Urinary excretion of NO3_- and cyclic GMP was increased on the 10th day in the low-sodium group, as compared with the normal- and high-sodium groups. The urinary excretion of cyclic GMP was increased at the 8th week, and NO3_- showed a tendency to increase in the low-sodium group, as compared with the high-sodium group. An up- regulation of NO production may explain, at least in part, the antihypertensive effect of sodium restriction. (Hypertens Res 1997; 20: 57-60)

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