Regional vascular and hemodynamic effects of orally administered nisoldipine in conscious rats

This study examined the hemodynamic and regional vascular effects of orally administered nisoldipine, a new dihydropyridine derivative (0.3 mg/kg) in normal conscious rats (n = 10). Nisoldipine significantly reduced systemic vascular resistance (0.58 to 0.38 mm Hg kg min/ml, p less than 0.05) and mean arterial pressure (122 to 108 mm Hg, p less than 0.05), and increased heart rate (395 to 447 beats/min, p less than 0.01) and cardiac index (225 to 326 ml/beat/kg, p less than 0.05). Left ventricular end-diastolic pressure was slightly decreased by nisoldipine (9.6 to 3.8 mm Hg, p less than 0.05). Blood flow (radioactive microspheres, 15 +/- 5 micron in diameter) to heart, gut, kidney, and brain was significantly increased. Improvement of blood flow was most pronounced in the coronary circulation (+ 58%) followed by the gut and renal circulatory beds. We conclude that nisoldipine represents a new orally effective calcium antagonist with highly selective effects in vascular smooth muscle as compared with its direct cardiac effects. The results are compared with our previous study utilizing intravenous nisoldipine.