Differential antagonism by Bay K 8644 of vasodilator effects of nifedipine, diltiazem, nicorandil and nitroglycerin in dog femoral circulation.

1. The modification by Bay K 8644 of the vasodilator effects of nifedipine, diltiazem, nicorandil and nitroglycerin was investigated in the femoral arterial bed of anaesthetized dogs. 2. The right femoral artery was cannulated and its arterial bed was perfused with autologous blood at a constant pressure slightly higher than the mean systemic arterial blood pressure. Bay K 8644 was infused intra-arterially (i.a.) and the 4 vasodilators were injected i.a. as bolus doses. 3. The vasodilator effects of nifedipine (0.3-10 nmol), diltiazem (0.01-1 mumol), nicorandil (0.1-10 mumol) and nitroglycerin (0.3-100 nmol) were all suppressed by infusions of Bay K 8644 (3-100 nmol min-1). 4. The dose-response curve of nifedipine was shifted parallel to the right by the infusion of Bay K 8644 and the dose-ratio was the greatest of the 4 drugs. 5. The dose-response curve of diltiazem was also shifted to the right by Bay K 8644. However, the dose-ratio was far smaller than that of nifedipine. 6. The vasodilator effect of nicorandil was not antagonized as much by Bay K 8644 as that of nitroglycerin. This less effective antagonism of nicorandil by Bay K 8644 can be explained if nicorandil, which although structurally a nitrate, can in addition cause relaxation of vascular smooth muscle by hyperpolarizing the membrane which would result in Bay K 8644 being less effective.