Abstract
Regional vascular responses to NKY-722 (NKY), a novel dihydropyridine derivative calcium channel blocker, and the effects on the responses to endothelin (ET) were investigated using tracer microspheres with a reference sample method in anesthetized rats. Intravenous injections of NKY, 0.2 and 2mg/kg, decreased blood pressure and total peripheral resistance dose-dependently. Cardiac index significantly increased only with the high dose regardless of bradycardia. Regional blood flow significantly changed with NKY: It increased in the brain, brown adipose tissue (BAT), intestine, colon and skin, but decreased in the liver, spleen, kidneys, adrenals and skeletal muscle. NKY decreased the regional vascular resistance in the brain, heart, lungs, BAT, intestine, colon and skin, but increased it in the liver, spleen and skeletal muscle. ET significantly increased blood pressure, but this was abolished by pretreatment with the low and high doses of NKY. Cardiac index became significantly lower with ET, and was not affected by NKY. Total peripheral resistance after ET remained lower with NKY pretreatments. ET decreased the blood flow mainly in the liver, spleen, kidneys, adrenals, BAT, intestine, colon, and skeletal muscle. Pretreatments with NKY prevented the decrease of flow caused by ET in the kidneys, adrenals, BAT, intestine, colon and skeletal muscle. These findings indicate that NKY lowers blood pressure mainly by decreasing the peripheral vascular resistance, and that NKY blunts many, but not all, endothelin effects on vasculature. (Hypertens Res 1994; 17: 29-34)
