Comparative renal effects of calcium channel blockers in conscious spontaneously hypertensive rats.
Five calcium channel blockers with diverse chemical structures were studied for potential renal selectivity after oral administration of a single dose to conscious spontaneously hypertensive rats. Nitrendipine (3 and 10 mg/kg) and diltiazem (30 and 100 mg/kg) caused significant increases in sodium and water excretion. In comparison, prenylamine (100 and 300 mg/kg) and flunarizine (100 and 300 mg/kg) failed to augment sodium and water excretion. Verapamil caused significant natriuresis only at 30 mg/kg. These data suggest that the diuretic and natriuretic action is not a common property of all calcium channel blockers. Pretreatment with SCH 23390 (20 mg/kg), a dopamine DA1 antagonist, selectively attenuated the diuresis and natriuresis induced by high doses of diltiazem (100 mg/kg) and nitrendipine (10 mg/kg) without blocking the renal responses to hydrochlorothiazide (1 mg/kg). Similarly, reserpinization abolished the renal but not the hypotensive action of diltiazem. Pretreatment with indomethacin (10 mg/kg), a cyclooxygenase inhibitor also significantly attenuated the diuresis and natriuresis elicited by diltiazem (100 mg/kg). These data suggest that intact dopamine and prostaglandin systems in the kidney are required for optimal expression of the renal effects of diltiazem and nitrendipine.
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D001552:Benzazepines / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002395:Catecholamines / Q000502:physiology; D004298:Dopamine / Q000502:physiology; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D012079:Renal Circulation / Q000187:drug effects*; D012110:Reserpine / Q000494:pharmacology; D013997:Time Factors
D014150:Antipsychotic Agents; D001552:Benzazepines; D002121:Calcium Channel Blockers; D002395:Catecholamines; D012110:Reserpine; D004298:Dopamine; D007213:Indomethacin