Amlodipine suppressed cardiac gene expression of brain natriuretic peptide, transforming growth factor-ß1 and fibronectin mediated by aldosterone in male stroke-prone spontaneously hypertensive rats.

OBJECTIVES: Amlodipine, a calcium channel blocker (CCB), is one of the most common antihypertensive medicines in Japan. We evaluated whether the calcium channel blocker confers cardiac protection through the renin-angiotensin-aldosterone system in male stroke-prone spontaneously hypertensive rats (SHR-SP). METHODS: Fifteen week-old rats were divided into 2 groups: amlodipine group (3 mg/kg/day, n = 5) and control group (n = 5). KEY FINDINGS: The CCB lowered systolic blood pressure significantly (P < 0.05). Plasma aldosterone concentration in the amlodipine group was remarkably lower than in the control group (P < 0.05), but plasma renin activity and plasma angiotensin II concentration were not different between the two groups. The CCB also suppressed the mRNA expression of brain natriuretic peptide, transforming growth factor-ß1, and fibronectin extracted from the left ventricle. CONCLUSIONS: These results suggest that amlodipine attenuates cardiac damage by lowering plasma aldosterone concentration in hypertensive rats with developing arteriosclerosis.

Oxidative stress in the Dahl salt-sensitive hypertensive rat.

Oxidative stress has been proposed as important in the pathogenesis of hypertension. Measurement of 8-iso prostaglandin F2alpha (8-ISO) is introduced for evaluating oxidative stress in vivo. 8-ISO is the major urinary metabolite of F2-isoprostanes and is formed nonenzymatically from the attack of superoxide radicals on arachidonic acid. We examined the oxidative stress level in the Dahl salt-sensitive (Dahl-S) rats and the Dahl salt-resistant (Dahl-R) rats. Dahl-S and Dahl-R rats were fed either a high salt diet (8% NaCl; HS) or low salt diet (0.3% NaCl; LS) for 3 weeks, and systolic blood pressure (SBP) and 24-hr urinary excretion of 8-ISO (U-8-ISO) were measured. In Dahl-S rats, the high salt diet induced hypertension (139 +/- 3 mmHg in LS versus 186 +/- 2 mmHg in HS, p < .05) and significantly increased the U-8-ISO (24.9 +/- 3.6 ng/24 hr in LS versus 63.2 +/- 14.6 ng/24 hr in HS, p < .05). No significant difference in blood pressure or U-8-ISO was observed between high-salt and low-salt treated Dahl-R rats. U-8-ISO concentration was correlated with SBP in all four experimental groups (r = 0.866). Moreover, urinary 8-hydroxy-2'-deoxyguanosine (U-8-OHdG), which is one of the most commonly used markers for evaluation of oxidative stress, was higher in Dahl-S-8% rats than in Dahl-S-0.3% rats (136.1 +/- 48.4 ng/24 hr in LS versus 322.8 +/- 46.7 ng/24 hr in HS, p < .05), and U-8-OHdG was correlated with SBP (r = 0.681) in Dahl-S rats. These results suggest oxygen radicals are involved in the pathogenesis of hypertension.

Different effects of L-type and L+N-type calcium channel blockers on hamster cheek pouch venules.

Dihydropyridine calcium channel blockers are not uniform in terms of their action on calcium channel. L-type calcium channel blockers dilate the resistance arterioles. Cilnidipine is a dihydropyridine calcium channel blocker that also acts on N-type calcium channels, and may dilate venules through its effect on the sympathetic receptor. The influence of an L-type calcium channel blocker (nifedipine) or this L+N type blocker at 10(-7) mol to 10(-4) mol on venular diameter was examined by superfusion of male Syrian hamster cheek pouches. Nifedipine dose dependently dilated the arterioles alone, whereas cilnidipine dilated both arterioles and venules. Application of 10(-7) mol omega conotoxin, an inhibitor of N-type channels, after nifedipine led to significant dilation of venules, while it had no influence when administered after cilnidipine. These findings indicate that the effects of calcium channel blockers on the venules differ according to the action on N-type calcium channels, and that cilnidipine (an L+N type calcium channel blocker) dilates venules through its additional action on N-type channels.