STUDIES ON A NEW 1, 5-BENZOTHIAZEPINE DERIVATIVE (CRD-401)

VI. EFFECTS ON RENAL BLOOD FLOW AND RENAL FUNCTION

Abstract

Effects of a new coronary vasodilator, CRD-401, on renal blood flow and renal function were investigated in anesthetized dogs. Renal arterial or systemic administration of the compound produced an increase in renal blood flow. The increase in renal blood flow induced by CRD-401 was not affected by pre-treatment with propranolol, atropine or dephenhydramine. Renal arterial administration of CRD-401 exhibited an antagonistic effect on the vasoconstricting action of angiotensin-II, whereas it had no effect on that of epinephrine. When infused continuously into the renal artery, CRD-40l increased the urine flow and sodium excretion as well as renal blood flow in all the conditions of fluid loading tested. The glomerular filtration rate was enhanced under saline loading but not under water diuresis. CRD-401 caused an increase in free water clearance. When the renal blood flow was kept constant with an aortic clamp during CRD-401 infusion, sodium excretion was significantly increased but no change was observed in glomerular filtration rate and PAH clearance. The results show that CRD-401 induced natriuresis was not entirely dependent upon the renal hemodynamic changes caused by the compound. By the stop-flow method, it was shown that the ratio of [urine sodium to plasma sodium] to [urine creatinine to plasma creatinine] increased in the distal portion of the nephrun by CRD-401 infusion. The present results indicate that the natriuretic action of CRD-401 is not only due to the changes in renal hemodynamics but it also may be ascribable to a direct effect of CRD-410 on the sodium reabsorption in the distal part of the nephron.