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Captopril potentiates the effects of nitroglycerin in the coronary vascular bed
I T Meredith1, J F Alison, F M Zhang
1Cardiology Department, Monash Medical Centre, Clayton, Victoria, Australia.
Objectives:
This study was designed to examine the effects of captopril on the coronary vascular responses to nitroglycerin.
Background:
The vasodilator effects of nitroglycerin are mediated by sulfhydryl-dependent bioconversion and influenced by local and systemic neural and hormonal counter-regulatory factors.
Methods:
In patients with angina pectoris, the effects of 10 days of treatment with the sulfhydryl-containing angiotensin-converting enzyme inhibitor captopril on the coronary vasodilator responses to intracoronary nitroglycerin (1- to 20-micrograms doses) were examined utilizing a double-blind, placebo-controlled, randomized design. The effects of captopril on the induction of nitroglycerin tolerance were also examined after a 20-h intravenous infusion of nitroglycerin.
Results:
Captopril reduced mean arterial pressure at rest by 8 mm Hg compared with 3 mm Hg in the placebo group (p = NS) and did not affect baseline coronary blood flow (168 vs. 144 ml/min in the placebo group, standard error of the differences of means (SED) 26) or coronary vascular resistance (53 vs. 57 dynes.s.cm-5, SED 9). Intracoronary nitroglycerin increased coronary blood flow in a dose-dependent fashion in both the captopril and placebo groups (p < 0.001). However, captopril potentiated the effects of all doses of nitroglycerin and shifted the dose-response relationship to the left (p < 0.001). At the maximal dose of 20 micrograms, intracoronary nitroglycerin increased the coronary blood flow by a further 60% in the captopril group compared with placebo. After 20 h of intravenous nitroglycerin (24 +/- 3 micrograms/min), the coronary vasodilator responses to intracoronary nitroglycerin were attenuated (p < 0.02) in the placebo group. However, the responses to intracoronary nitroglycerin in the captopril group, remained similar to the responses observed before intravenous nitroglycerin exposure.
Conclusions:
Captopril potentiates the coronary vasodilator responses of nitroglycerin in both the absence and the presence of nitroglycerin tolerance. The mechanisms and therapeutic implications of this interaction require further exploration.