In several models of angiotensin II (ANG II) dependent hypertension, intrarenal ANG II levels increase to a much greater extent than the circulating levels even though the renal renin levels are decreased. The 2-kidney-1-clip (2K1C) Goldblatt rat model is particularly intriguing because hypertension develops in the presence of an intact kidney which would be expected to maintain sodium balance and protect against hypertension. Although the non-clipped kidney becomes renin depleted, it exhibits enhanced microvascular reactivity and increased tubular fractional sodium reabsorption. The non-clipped kidney ANG II content is either elevated or unchanged and proximal tubular fluid ANG II concentrations are not suppressed compared to the nanomolar concentrations found in normal rats. These results suggest that intrarenal ANG II content can be regulated independently of renal renin content. A similar hypertensive process occurs in rats infused chronically with low doses of ANG II. Renal ANG II content increases over 14 days to a greater extent than the circulating concentrations. Functionally, ANG II infused rats demonstrate reduced sodium excretion and marked suppression of pressure natriuresis. These ANG II dependent influences on kidney function contribute to the maintenance of hypertension. Renal augmentation of ANG II, hypertension, and suppressed sodium excretion are blocked by AT, receptor blockers. To study the mechanisms responsible for intrarenal ANG II augmentation, we infused a different form of ANG II (Val⁵ ANG II), that can be separated from endogenous ANG II by HPLC. These results indicated that the increased renal ANG II content was due to accumulation of circulating ANG II in addition to continued production of endogenous ANG II. The renal accumulation of Val⁵-ANG II was markedly reduced by concomitant treatment with the AT₁ receptor blocker, losartan. In addition, we found an unchanged overall ANG II-AT₁ receptor protein which probably contributes to the maintained ANG II dependent influences. Collectively, the data support the concept that there is internalization of ANG II through an AT, receptor mediated process and that some of the internalized ANG II is protected from degradation. The augmented intrarenal ANG II coupled with sustained levels of AT, receptors contribute to the continued ANG II dependent suppression of renal function and sodium excretion thereby maintaining the hypertension. (Hypertens Res 2000; 23: 291-301)

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The purpose of this study was to clarify the relationships between obesity (BMI) and BP levels, leptin levels, sympathetic activity, and insulin sensitivity in a Japanese male population. In 912 young, non-diabetic, Japanese men with a wide range of BMI (16.5-33.6kg/m²), blood pressure (BP), fasting plasma norepinephrine (NE), insulin and leptin levels were measured after an overnight fast. The cohort consisted of 603 normotensive and 309 hypertensive subjects. The study was carried out using a cross-sectional design. When the subjects were subdivided by tertile in relation to BMI, the 101 subjects in the heaviest group (BMI>27.9kg/m²) had a significantly higher systolic BP (p<0.05) and pulse rate (p<0.05) as well as higher NE (p<0.01), insulin (p<0.01), and leptin (p<0.01) levels than 86 subjects in the leanest group (BMI<22.2kg/m²). In the whole cohort, BMI correlated with mean BP (p<0.01), plasma NE (p<0.05), insulin (p<0.001) and leptin (p<0.001). The mean BP correlated with BMI (p<0.001), plasma NE (p<0.01), insulin (p<0.01) and leptin (p<0.05). Plasma leptin levels correlated with fasting plasma insulin levels (p <0.05), but not with plasma NE levels (NS). As analyzed by multiple regression analysis, only plasma NE (p<0.05) and BMI (p<0.001), but not plasma insulin levels, were significant, independent predictors of BP levels (r²=0.125, F=10.51, p=0.0001). These results suggest that obesity (BMI) and heightened sympathetic nervous system activity contribute to BP elevation (hypertension). (Hypertens Res 2000; 23: 303-310)

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The spectral power of heart rate variability has been shown to be negatively correlated with left ventricular mass (LVM), suggesting the contribution of left ventricular hypertrophy to autonomic dysfunction in essential hypertension. However, a simultaneous assessment of autonomic function and ambulatory blood pressure in relation to LVM has not been carried out. The objective of the present study was to elucidate the synergistic effects of ambulatory blood pressure and autonomic nerve activity on the heart. We enrolled 25 ambulant patients with untreated essential hypertension (9 men and 16 women; mean age 50.6±2.0 years). The ambulatory blood pressure and heart rate variability were simultaneously monitored every 30min for 24h. The spectral power of high-frequency (HF: 0.15 to 0.4Hz) and low-frequency (LF: 0.05 to 0.15 HZ) bands were measured, and the ratio of LF to HF (LF/HF) was calculated. LF/HF and HF were used as indexes of sympathetic and parasympathetic activities, respectively. LVM was determined by echocardiography. Both the average daytime and nighttime systolic ambulatory blood pressures significantly correlated with the LVM index (r=0.644, p<0.001; and r=0.428, p<0.05; respectively), although there was no such correlation with the clinic blood pressures. In contrast, a single reading of ambulatory systolic blood pressure measured when LF/HF reached a maximum value was significantly correlated with the LVM index independently of age and sex (partial r=0.484, p<0.05). These results suggest that the ambulatory systolic blood pressure during increases in the activity of the sympathetic nervous system is able to infer LVM in essential hypertension. (Hypertens Res 2000; 23: 311-316)

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Angiotensin-converting enzyme (ACE) inhibitors are known to be the most effective antihypertensive drugs for reducing left ventricular mass in hypertensives when compared to other classes of drugs. In the present study, we evaluated the effects of imidapril, an ACE inhibitor, on serum procollagen type III amino-terminal peptide (PIIIP) levels as well as the left ventricular mass index (LVMI). The subjects consisted of 15 patients (12 men and 3 women) in the outpatient clinic of our hospital who were diagnosed as essential hypertensives and who had not been treated with any antihypertensive medication prior to the study. Left ventricular hypertrophy was observed in all of the patients, i.e., LVMI>110g/m² in men and >106g/m² in women. Blood pressure, LVMI, and serum PIIIP levels were measured before and after treatment with imidapril for 6 months. The starting dose of imidapril was 5mg, and this was increased to 10mg. Finally, 1 mg of trichlormethiazide was added to obtain adequate control of blood pressure. Blood pressure significantly decreased in 12 patients, and the mean LVMI decreased significantly from 153.1±9.0 to 135.4± 6.3 (p<0.01) after treatment. The changes in LVMI and PIIIP levels with treatment had significant correlation (r=0.639, p<0.05). The present study showed that imidapril reduces the left ventricular mass in hypertensives after 6 months of treatment, and that this may at least in part be due to a decrease in the collagen content of the hypertrophied heart, suggesting that serum PIIIP levels are a useful marker of the regression of left ventricular hypertrophy. (Hypertens Res 2000; 23: 317-322)

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Although it has been suggested in several reports that 24-h ambulatory blood pressure (BP) is a better predicter than casual BP measured in a clinician's office of the incidence of cardiovascular (CV) events, little information is available concerning the prognostic value of nighttime BP in the elderly population. Therefore, to evaluate the clinical implications of the nighttime BP in the elderly, we prospectively followed-up 324 elderly individuals (mean age, 77.2±7.0 years) who had undergone ambulatory BP monitoring at an annual health examination over a mean follow-up period of 51.5±22.0 months, and the relationship between BP and CV events was analyzed using Cox's proportional hazard model. For the analysis, 310 participants, excluding 14 subjects who were withdrawn due to non-CV events, were classed into two groups, one consisting of 134 individuals who were undergoing treatment with an anti-hypertensive drug (medicated group) and another consisting of 176 who were not medicated (nonmedicated group). New cardiovascular events developed in 43 cases in the medicated group and in 14 cases in the non-medicated group during the follow-up period. In the medicated group, a linear relationship was observed between BP and the event rates. The hazard ratio for CV events adjusted for age, sex, and other cardiovascular risks was 1.28 (95% confidence interval [CI], 1.05 to 1.54, p<0.05) for a 10mmHg increase of 24-h systolic BP. Corresponding values in 24-h diastolic BP, nighttime systolic BP, and nighttime diastolic BP were 1.71 (1.19 to 2.46, p<0.01), 1.34 (1.13 to 1.58, p<0.01), and 1.67 (1.20 to 2.31, p<0.01), respectively. In the non-medicated group, the event rate was least in the subgroup in the second-lowest quartile for nighttime systolic BP, with a slight non-significant increase in the subgroup of the lowest quartile. It was shown that insufficient control of nighttime BP in the elderly with hypertension is associated with the development of CV complications. (Hypertens Res 2000; 23: 323-330)

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Our objective was 1) to assess postischemic vasodilatation using simultaneous intravascular two-dimensional and Doppler ultrasound, and 2) to clarify whether plasma nitrite and nitrate (NO_x^-) levels change during postischemic vasodilatation. The vascular cross-sectional area (GSA) was evaluated in 18 mongrel dogs, and the average instantaneous peak velocity (APV) in the iliac arteries after the 5-min occlusion of blood flow was determined. Plasma NO_x^- levels were measured at the baseline, during the occlusion of blood flow, and 1.5, 3, and 10min after recanalization. The %CSA significantly increased from 30s to 7 min after the recanalization, and maximal vasodilatation was observed at 1.5min after the recanalization (14.1±0.9 to 15.8±1.0mm², p<0.0001 vs. baseline). Plasma NO_x^- levels were significantly reduced during the occlusion of blood flow and remained reduced at 1.5, 3, and 10min after recanalization compared with the baseline values. We concluded that simultaneous intravascular two-dimensional and Doppler ultrasound is useful for assessment during postischemic vasodilatation, and that plasma NO_x^- levels assayed with the Griess reagent do not significantly increase, even when maximal vasodilatation is observed. (Hypertens Res 2000; 23: 331-338)

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Cardiovascular responses to L-arginine and nitric oxide (NO) are augmented in the rostral ventrolateral medulla (RVLM) of spontaneously hypertensive rats (SHR), and the intravenous injection of superoxide dismutase (SOD) mimetic decreases the arterial pressure in these rats. In the present study, we examined whether the chronic central infusion of L-arginine or an SOD mimetic would reduce the blood pressure of SHR and alter responses to an NOS inhibitor or an NO donor in the RVLM. For this purpose, we administered L-arginine (SHR-Arg: 13.2μmol/day, n=6), a stable membrane-permeable SOD mimetic, 4-hydroxy-2, 2, 6, 6-tetramethyl piperidine-1-oxyl (tempol) (SHR-Temp: 13.2μmol/day, n=6), or vehicle (SHR-C: n=6) into the lateral ventricle of 12-week-old SHR for 2 weeks. When the rats reached 14 weeks of age, N^G-nitro-L-arginine methyl ester (L-NAME: 10nmol/50nl) or NOC 18 (NO donor: 10nmol/50nl) was microinjected into the unilateral RVLM. Blood pressure did not decrease in any of the treatment groups (SHR-Arg: 209± 4mmHg, SHR-Temp: 210±6mmHg, SHR-C: 197±6mmHg). The microinjection of L-NAME into the RVLM induced a significant increase in the mean arterial pressure (MAP) (SHR-Arg: 10-4mmHg, SHR-Temp: 12± 4mmHg, SHR-C: 11±3mmHg), and the increases in MAP did not differ among the groups. The microinjection of NOC 18 reduced MAP (SHR-Arg: -12±2mmHg, SHR-Temp: -15±3mmHg, SHR-C: -13±3 mmHg), and the depressor responses were comparable among groups. These results do not support the hypothesis that chronic L-arginine deficiency or the enhanced degeneration of NO by superoxide radicals in the central nervous system contributes to the maintenance of arterial pressure in SHR. (Hypertens Res 2000; 23: 339-343)

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Previous studies have suggested the prognostic significance of left ventricular (LV) geometric patterns in essential hypertension. However, the relation between cardiomyocyte functional changes and LV geometric patterns has not been clarified. This study was designed to assess the morphological and functional changes in isolated myocytes derived from different LV geometric patterns in hypertension. After 2-3 weeks of a high-salt (8%) diet from the age of 6 weeks, 20 Dahl salt-sensitive (DS) rats were classified into the following three groups on the basis of an echocardiographically determined LV mass index and the relative wall thickness: concentric hypertrophy (11), eccentric hypertrophy (4), and concentric remodeling (5). Ten Dahl salt-resistant (DR) rats served as controls. In vivo LV functions were assessed based on echocardiographic measurements. We examined ventricular myocytes isolated from all groups. To evaluate the force-frequency relation, cardiomyocytes isolated from all groups were paced at stimulation rates of 0.3, 0.5, 1.0, 2.0, and 3.0Hz. Concentric hypertrophy and eccentric hypertrophy groups exhibited an increase in myocyte width but no changes in the length. Concentric hypertrophy and concentric remodeling groups demonstrated in vivo LV dysfunction. In addition, DS rats, especially these with concentric hypertrophy, demonstrated impaired frequency responses in terms of both myocyte contraction and relaxation compared with DR rats. This impaired force-frequency relationship was especially remarkable at high frequencies. These findings suggest that the structural and functional changes in cardiomyocytes are closely related to the LV geometric pattern and may contribute to a different prognosis according to different geometric patterns. (Hyperfens Res 2000; 23: 345-351)

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Recent studies suggest that some of the beneficial effects of 3-hydroxyl-3-methylglutaryl (HMG)-CoA reductase inhibitors such as pravastatin may be through their cholesterol-lowering independent effects on the blood vessels. We have recently reported that chronic inhibition of nitric oxide (NO) synthesis with N^ω-nitro-L-arginine methyl ester (L-NAME) increases systolic blood pressure and induces coronary vascular inflammatory changes in rats. We designed this study to investigate whether treatment with pravastatin attenuates such proarteriosclerotic changes through their cholesterol-lowering independent effects. Several groups of Wistar-Kyoto rats were studied: the control group, L group received L-NAME in their drinking water (100mg/kg per day) and L+Px group received L-NAME plus pravastatin (50, 100 or 250 mg/kg per day). We observed marked increases in monocyte infiltration into the coronary arteries, proliferative cell nuclear antigen-positive cells, and monocyte chemoattractant protein-1 (MCP-1) expression in the heart on day 3 after L-NAME administration began. Treatment with pravastatin did not affect serum cholesterol levels or systolic blood pressure but did reduce the L-NAME induced inflammatory and proliferative changes. Pravastatin also attenuated the MCP-1 gene expression induced by L-NAME. In summary, pravastatin inhibited the inflammatory and proliferative changes in the coronary vessels through their cholesterol-independent effects in this model, which may provide an insight into the mechanisms of anti-inflammatory or anti-arteriosclerotic actions of pravastatin. (Hypertens Res 2000; 23: 353-358)

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It has been suggested that nitric oxide (NO) influences the actions of L-glutamate and angiotensin II in the brain. In the present study, we examined whether cardiovascular responses to L-glutamate and angiotensin II would be altered in the rostral ventrolateral medulla (RVLM) of rats treated with an NO synthase inhibitor, N^G-nitro-L-arginine methyl ester (L-NAME). Wistar rats were treated with either L-NAME (100 mg/kg/day, n=9) or vehicle (n=8) for 4 weeks. L-glutamate (2 nmol/50nl) or angiotensin II (100pmol) was then microinjected into unilateral RVLM of anesthetized rats. Upon completion of the experiments, angiotensin-converting enzyme (ACE) activity of the brain stem was measured. The systolic blood pressure after 4 weeks of the treatment was significantly higher in the L-NAME group (203± 8mmHg) than in the control group (142±3mmHg, p<0.01). The pressor response to L-glutamate microinjected into the RVLM was significantly greater in the L-NAME group (31±2mmHg) than in the control group (24±1 mmHg, p<0.01). Similarly, angiotensin II showed a greater pressor response in the L-NAME group. ACE activity of the brain stem did not differ between the groups. In conclusion, NO may have an inhibitory influence on the actions of L-glutamate and angiotensin II in the RVLM. (Hypertens Res 2000; 23: 359-364)

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To compare the efficacy and sensitivity of heart rate variability (HRV), QT dispersion (QTd) and ventricular late potential (VLP) examination in judging autonomic function. Thirty three patients with acute myocardial infarction (AMI) and 33 patients with diabetes mellitus (DM), all of whom were diagnosed with autonomic neuropathy determined by a standard test of cardiovascular autonomic function, were examined by HRV (timing domain methods), QTd and VLP. Thirty three normal individuals served as controls. The mean SD of the normal R-R interval (SDNN) in both the AMI and DM groups was significantly less than that in the control group (p<0.01); and of course, the QTd of these groups was significantly greater than that of the controls (p<0.01). The VLP positive rate of the AMI and DM groups were much higher than that of the control group (p<0.001). SDNN was shown to be significantly negatively correlated to QTd (r=-0.45); and significantly negatively correlated to VLP (r=-0.47); QTd was shown to be positively, though not significantly, correlated to VLP (r=0.48). QTd could be looked as sieving index; HRV could be looked as routine examination of cardiovascular autonomic function, especially SDNN; the combination of HRV and VLP could improve the accuracy of diagnosis. (Hypertens Res 2000; 23: 367-370)

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To study the relation between left ventricular geometric alteration and extracardiac target organ damage in hypertensive patients. A retrospective study of 298 patients with essential hypertension was performed. Left ventricular mass index (LVMI) and relative wall thickness (RWT) were calculated using echocardiographic data. Patients were divided into four groups based on their left ventricular geometric pattern as determined using LVMI and RWT. Each of the four left ventricular geometric patterns was associated with a different degree of extracardiac organ damage. In multivariate analysis, LVMI and RWT showed strong, significant correlation to retinal changes and increases in serum creatinine levels, respectively. Alteration of left ventricular geometry resulted in an increase in the degree of extracardiac target organ damage. Echocardiograghic classification of left ventricular geometry can further stratify hypertensive patients according to risk, and possibly according to the indications for intensive treatment. (Hypertens Res 2000; 23: 371-376)

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To investigate the relationship between hypertensive left ventricular hypertrophy (LVH) and levels of endothelin (ET) and nitric oxide (NO), and to provide an experimental basis for prevention and treatment of hypertensive LVH. Fifty eight hypertensive patients and 14 healthy controls were studied. All patients were examined by echocardiography. Left ventricular mass (LVM) and left ventricular mass index (LVMI) were calculated using Devereux RB formula. Hypertensive patients were divided into a LVH (+) group (n=21) and a LVH (-) group (n=37), and the levels of endothelin and nitric oxide in the peripheral venous blood were measured. The mean ET level was significantly higher in the LVH (+) group than in LVH (-) group (p <0.05), but the NO level was significantly lower in the LVH (+) group. The ET/NO ratio was significantly higher in the LVH (+) group than in LVH (-) group (p<0.01). For the stepwise multiple regression analysis, the LVMI of hypertensive patients served as a dependent variable, and age, sex, BMI, MAP, ET, NO, and ET/NO served as independent variables. Only MAP, ET, and NO were found to have significant correlation to hypertensive LVH. ET had a significant positive correlation, and NO a significant negative relation to LVMI, but ET/NO showed no correlation to hypertensive LVH. ET and NO are involved in hypertensive LVH; the independent action of ET and NO in the pathogenesis of hypertensive LVH may weaken the relation between ET/NO and hypertensive LVH. (Hypertens Res 2000; 23: 377-380)

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The effects of heparin and low molecular weight heparin (LMWH) on the growth of cultured human aortic smooth muscle cells (hASMCs) were studied. The fourth-passage hASMCs were planted onto a 24-well plate (5 wells for each concentration of heparin or LMWH) and cultured by DMEM containing 5% either old or fresh human serum (HS), 10% fetal calf serum (FCS), and differing concentrations of heparin or LMWH (heparin and LMWH were presented as hexuronic acid) together with corresponding control groups (with-out heparin or LMWH) for 24h. hASMCs growth was estimated both morphologically and by 3H-TdR incorporation. The results revealed that both heparin and LMWH inhibited the proliferation of healthy growth hASMCs, but promoted the proliferation of weak growth hASMCs. These results suggest for the first time that heparin and LMWH have a dual regulative role (inhibition and promotion) in hASMCs growth and indicate that they may play an important role in controlling the proliferation of vascular smooth muscle cells and maintaining the integrity of vascular structure. (Hypertens Res 2000; 23: 381-384)

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The renin-angiotensin system (RAS) plays a very important role in the regulation of blood pressure and electrolyte homeostasis in mammals. It has also been hypothesized to regulate local tissue and organ blood supply in an autocrine/paracrine manner. To further study RAS physiology, transgenic mice carrying the human renin gene were produced by microinjection and were screened by PCR. The human renin transgene was found, by RT-PCR, to be expressed in the heart, kidney, and lung of transgenic mice, but not in the liver or skeletal muscle. The mean levels of renin activity in various tissues were determined by radioimmunoassay. The mean level of renin activity in the plasma and the heart/body weight ratio of the transgenic mice (n=7) were also found to be significantly higher (p<0.05) than those of the control mice (n=8). However, no significant differences were seen in the mean levels of renin activities in the kidney and heart between transgenic and control mice. Thus, the transcription of human renin gene in transgenic mice is regulated in a tissue-specific manner. This transgenic model will be useful in clarifying the regulatory mechanisms of the renin gene and the relationship between this gene and diseases. (Hypertens Res 2000; 23: 385-389)

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The present study compared renoprotective effects of angiotensin II type I receptor antagonist (AT₁RA) with angiotensin converting enzyme inhibitor (ACEI), and their influence on the renin-angiotensin-system (RAS). Experimental nephrotic syndrome was induced in SD rats by repeated peritoneal injections of puromycin. Twenty-eight rats were randomly divided into four groups: normal control, nephrotic control, ACEI-treated, and AT₁RA-treated groups. Serum, urine, and renal tissue were collected for study at the end of 12 weeks. Compared with those of the nephrotic control group, urinary protein was less and renal function was better in both treated groups. The glomerular and interstitial damage indexes of both ACEI- and AT₁RA-treated rats were lower than those of nephrotic control rats, with no significant difference observed between the two treated groups. Local renal ACE activity and angiotensin II concentration were elevated in nephrotic rats (p<0.01). However, there is no significant difference in circulating RAS, renal tissue renin, and aldosterone between the normal control and nephrotic control rats. As expected, enalapril inhibited the local renal ACE activity and significantly decreased angiotensin II (p<0.01). Intrarenal ACE activity and angiotensin concentration returned to normal levels after treatment with irbesartan (p<0.01). In conclusion, AT₁RA and ACEI have comparable renal protective effects, and these protective effects were associated with the inhibition of intrarenal ANG II. (Hypertens Res 2000; 23: 391-397)

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The replication and activation of both vascular smooth muscle cells and macrophages, which have previously entered the arterial wall, are key events in the atherosclerotic process. The importance of macrophage colony-stimulating factor (MCSF) in control of the growth/proliferation of both cell types confers to this compound a central role in the development of vascular lesions. In order to gain insight into the mechanisms of macrophage proliferation, we investigated the effect of MCSF upon the proliferation of DEL cells. DEL cells constitute a monocyte/histiocytic cell line that differentiates along a macrophage lineage following exposure to phorbol ester. DEL cells constitutively express MCSF, and its receptor MCSFR is encoded by c-fms. We examined whether MCSF might play a role in the proliferation of cultured DEL cells. [³H] Thymidine or 5-bromo-2-deoxyuridine (BrdU) incorporation was measured following the addition of recombinant MCSF or L929 cell supernatant (as a source of MCSF) to quiescent DEL cells. In DEL cells, serum-free L929 cell supernatant induced DNA synthesis in a dose-dependent manner, and such an effect could be blunted by pretreatment of L929 cell supernatant with anti-mouse MCSF antibody. In these cells, DNA synthesis could also be triggered in a dose-dependent manner by the addition of recombinant human MCSF (rh MCSF) or thrombin. These findings clearly show that MCSF influences DEL cell proliferation and suggest an autocrine loop activation. They indicate that MCSF plays an important role in the development of vascular lesions, which occur during atherosclerotic progression. (Hypertens Res 2000; 23: 399-401)

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The abnormal proliferation of vascular smooth muscle cells (VSMCs) is closely related to vascular diseases. There is growing evidence that calcium antagonists inhibit VSMC growth/proliferation, yet their molecular mechanisms remain to be determined. Recent reports suggest that p42/p44 mitogen-activated protein kinases (MAPKs) play an important role in cell growth and proliferation induced by growth factors. This study was designed to determine whether these MAPKs are involved in VSMC proliferation induced by basic fibroblast growth factor (bFGF) and to examine the inhibitory effect of amlodipine. Human VSMCs were obtained from inner mammary artery. p42/p44 MAPKs activity was measured by immunoblotting assay using anti-p42/p44 phospho-MAPK antibody. 1) bFGF (20ng/ml) significantly activated p42/p44 MAPKs with a peak time of 5-15min, which was maintained for 3h. PD98059 (100nM-10μM), a specific inhibitor of MAPK kinase, inhibited bFGF-induced p42/p44 MAPKs activation in a dose-dependent manner. 2) Amlodipine (1-100nM) dose-dependently inhibited p42/p44 MAPKs activation by bFGF. 3) Amlodipine (10nM) could inhibit both short-term and long-term p42/p44 MAPKs activation by bFGF. Our results indicate that bFGF could activate p42/p44 MAPKs. Amlodipine, which could inhibit bFGF-induced human VSMC proliferation, inhibited both short-term and sustained p42/p44 MAPKs activation by bFGF, suggesting that bFGF-induced VSMC proliferation may be related to p42/p44 MAPKs activation, and that the antiproliferative effect of amlodipine may be related to its inhibition of p42/p44 MAPKs activation. (Hypertens Res 2000; 23: 403-406)

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