ABSTRACT
The effects of d-3-acetoxy-cis-2,3-dihydro-5-[2-(dimethylamino)ethyll-2-(p-methoxyphenyl)-1,5-benzothiazepine-4(5H)-one hydrochloride (diltiazem hydrochloride; CRD-401) on the hepatic, superior mesenteric and femoral arteries were investigated in dogs. The results obtained were as follows: 1. At an i.v. dose of 100 microgram/kg, CRD-401 lowered the mean aortic blood pressure (-5%). It also decreased the diastolic aortic blood pressure (-11%) but did not affect the systolic aortic blood pressure. 2. The mean aortic blood pressure decreased after injection of CRD-401, but the blood flows in the hepatic, superior mesneteric and femoral arteries increased to 33%, 31% and 17%, respectively, more than did the control values and the vascular resistances of these arteries decreased by 25%, 27% and 17%, respectively. The present study obviously demonstrates that CRD-401 has vasodilating action on the hepatic, superior mesenteric and femoral arteries.
Subject(s)
Benzazepines/pharmacology , Diltiazem/pharmacology , Hemodynamics/drug effects , Animals , Dogs , Femoral Artery/drug effects , Liver Circulation/drug effects , Mesenteric Arteries/drug effects , Regional Blood Flow/drug effects , Time FactorsABSTRACT
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.
