Abstract
Hypotensive effects of diltiazem hydrochloride (Dil) were examined in DOCA/saline hypertensive rats. Intravenous (10 ?? 300 μg/kg, under urethane anesthesia) or oral (3 ?? 100 mg/kg, in a conscious state) administration of a single dose of diltiazem (Dil) produced a dose-dependent decrease in blood pressure in DOCA/saline hypertensive rats as well as in uninephrectomized (saline loaded) and intact rats. In these experiments, fall in the blood pressure in DOCA/saline rats was 5 to 10 times greater than in other experiments where a different regimen was used. Furthermore, the development of hypertension in DOCA/saline rats was slightly suppressed by repeated oral dosing for 3 weeks of either Dil (15 mg/kg×2/day) or trichlormethiazide (TCM, 1 mg/kg×2/day). Combined administration of Dil and TCM (Dil 15 mg/kg+TCM 1 mg/kg) significantly suppressed the development of hypertension. A similar tendency was also observed when Dil and/or TCM were given orally for 10 successive days to DOCA/saline rats in which the systolic pressure was about 180 mmHg. It was found, however, that the pressor response to norepinephrine or angiotensin-II of DOCA/saline rats given Dil and/or TCM (for 3 successive weeks) was similar to that of control (non-drug-treated DOCA/saline rats), when comparisons were made after bilateral vagotomy and pentolinium treatment. These results indicate that the hypotensive effect of Dil is augmented with the concomitant administration of TCM and that this effect may not be the result of a reduction in the pressor response to norepinephrine or angiotensin-II.
