Effects of diltiazem Hydrochloride (CRD-401) on renal hemodynamics of dogs

The effect of d-3-acetoxy-cis-2,3-dihydro-5-[2-(dimethylamino)ethyl]-2-(p-methoxyphenyl)-1,5-benzothiazepine-4(5H)one hydrochloride (ditiazem hydrochloride, CRD-401) on renal hemodynamics was investigated in 18 mongrel adult dogs, and the following results were obtained. 1. Renal blood flow (RBF) was significantly increased following i.v. injection of 100 microgram/kg of CRD-401, in spite of decreased ao-tic blood pressure. Moreover the same dose of the drug elicited greater increase in RBF while the renal arteries were perfused at a constant pressure in order to prevent the decrease in systemic blood pressure from affecting RBF. These results suggest that CRD-401 has a vasodilatory action on the renal arteries. 2. The increasing rate of RBF and decreasing rate of renal vascular resistance (RVR) after injection of the drug into the renal artery at the dose level of 3 microgram/kg were found to diminish by pretreatment with hexamethonium (C6) before CRD-401. The vasodilating effect of CRD-401 on the renal arteries was therefore assumed to be more prominent in a state of renal arterial constriction. 3. RBF and RVR were increased and decreased, respectively, in proportion to the doses of CRD-401 ranging from 3 to 100 microgram/kg, the vasodilating action of CRD-401 on the renal arteries increased dose-dependently.