Natriuretic action of manidipine hydrochloride, a new calcium channel blocker, in spontaneously hypertensive rats.

Abstract

Abstract-Effects of manidipine, a new dihydropyridine derivative, on sodium and water excretion were examined in conscious spontaneously hypertensive rats. Manidipine (3 mg/kg) significantly increased the sodium and water excretion in the urine collected for 3 hr after the calcium antagonist was orally administered, and its natriuretic action was more prominent than those of nifedipine and nicar dipine (3 mg/kg). These results suggest that manidipine may be useful for treating hypertension.Manidipine (CV-4093.2HCI) shows potent and long-lasting antihypertensive action, dilates renal vasculature, and increases renal blood flow in spontaneously hypertensive rats (1, 2). The calcium antagonist also causes highly selective long-lasting inhibition of the calcium currents in the smooth muscle cells of the rabbit pulmonary artery but has little card iodepressant action (3, 4). In the present experiments, the effect of manidipine on urinary excretion of electrolytes and water was examined in spontaneously hypertensive rats. Male spontaneously hypertensive rats (SHR) of a stroke-prone strain were used at 10-11 weeks of age (systolic blood pressure: 205±2 (S.E.) mmHg; body wt.: 236±2 g). The rats were housed in groups of 5 to 7 animals in wire-mesh cages in a temperature and light-controlled room and were allowed free access to food and tap water. On the day of the experiment, the rats were fasted for 2 hr prior to saline loading. Calcium antagonists (manidipine hydrochloride, nifedipine, nicar dipine hydrochloride), synthesized in our Chemistry Research Laboratories, were sus pended in 5% arabic gum and orally adminis tered at the volume of 0.2 ml/100 g body wt.; and immediately after the drug administration, a volume of 0.9% saline equivalent to 2.5% of the body wt. was orally administered to the animals (n=5-7 in each group). After the saline loading, 3-hr urine samples were collected using metabolism cages. Sodium and potassium concentrations in urine were analyzed using flame photometry (Corning 455), and creatinine concentration in the urine was measured using an assay kit (Wako). The experiment was done twice, once with manidipine and nifedipine and once with nicardipine. A control was used in each experiment.As shown in Fig. 1, manidipine (3 mg/kg, p.o.) and nifedipine (3 mg/kg, p.o.) increased urinary volume to 270% and 217% of the value in the control group (0.90±0.20 ml/ 100 g body wt.), respectively, and also increased sodium excretion to 217% and 165% of the control value (150±4 /tEq/100 body wt.), respectively. The sodium excretion in the rats treated with manidipine was sig nificantly higher than that in rats treated with nifedipine. Nicardipine (3 mg/kg, p.o.) did not increase urinary volume (0.97±0.08 ml/ 100 g in the control and 0.98±0.1 2 ml/100 g in the treated group) or sodium excretion (161 ±27 uEq/ 100 g in the control and 160± 28 ,uEq/100 g in the treated group).Potassium excretion was not changed by treatment with any of the calcium antagonists (values in controls: 75±5 and 84±8 /tEq/100 g). Urina...

Electroencephalographic Evaluation of the Therapeutic Efficiency of Antihypertensive Agents on M‐shrsp

“…ACE1 decreases systemic vascular resistance and preserves cerebral blood flow auto regulation (Cushman et al 1987;Torup et al 1993). On the other hand, the protective effects of the calcium antagonist can be explained by vasodilator activity (Nagaoka & Shibota 1989). In the present experiment, the administration of SQ 29, 852 and manidipine resulted in normal EEG pattern recovery in rats with hypertension.…”

Manidipine Hydrochloride [CV‐4093(2HCl)]

“…Effects of manidipine on renal hemodynamics and function have been investigated in SHRs (42,43) and SPSHRs (34,35). After intravenous injection to anesthetized SHRs, manidipine produced a long-lasting hypotension associated with an increase in renal blood flow, indicating a renal vasodilator effect ( Fig.…”