Direct vascular and myocardial effects of nisoldipine.
The effects of the dihydropyridine calcium antagonist nisoldipine on vascular smooth muscle and myocardium were investigated by brachial artery infusions and measurements of forearm blood flow and by intracoronary infusions and measurements of maximal rate of rise of left ventricular pressure (dP/dtmax). Brachial artery infusions (0.1 to 16 micrograms/min/1,000 ml tissue) in 10 patients with essential hypertension increased forearm blood flow and decreased calculated forearm vascular resistance dose dependently (maximal reduction of forearm vascular resistance 88%). A comparison with the vascular effects of verapamil indicated that the vasodilator potency of nisoldipine is approximately 40- to 50-fold greater in this model supporting similar results from in vitro experiments. Coronary artery infusions of nisoldipine (12, 24 and 48 micrograms over 3 minutes each) in 9 patients undergoing diagnostic left-sided cardiac catheterization did not change dP/dtmax. This lack of effect on left ventricular contractility was similar in patients with normal or impaired left ventricular function. Even though the coronary artery concentrations during the infusion are unknown, the highest intracoronary dose was comparable to the highest brachial artery infusion. Since the coronary vasculature has been found to be at least as sensitive to nisoldipine as the peripheral vasculature, it can be assumed that nisoldipine has no negative inotropic effect even in dosages that probably induced marked vasodilation. Thus, for nisoldipine and possibly other new dihydropyridine calcium antagonists, the concept of a dissociation between peripheral vasodilatation and direct myocardial effects also seems to apply to human circulation and the heart.
Kiowski
W
W
Department of Medicine, University Hospital, Basel, Switzerland.
Pfisterer
M
M
Burkart
F
F
D000328:Adult; D000368:Aged; D001794:Blood Pressure / Q000187:drug effects; D001916:Brachial Artery; D002302:Cardiac Output / Q000187:drug effects; D003331:Coronary Vessels; D005260:Female; D006321:Heart / Q000187:drug effects*; D006801:Humans; D006973:Hypertension / Q000503:physiopathology; D007261:Infusions, Intra-Arterial; D008297:Male; D008875:Middle Aged; D015737:Nisoldipine / Q000008:administration & dosage / Q000494:pharmacology*; D012039:Regional Blood Flow / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects*; D014700:Verapamil / Q000494:pharmacology
D015737:Nisoldipine; D014700:Verapamil