In patients with severe coronary atherosclerotic disease, the angiotensin-converting enzyme inhibitor captopril attenuates the vasoconstriction induced by the cold pressor test and diving (two stimuli that cause reflex sympathetic activation) via removal of the facilitating effect of angiotensin II on sympathetic drive. However, whether calcium antagonists also have this effect is not clear. We evaluated the effects of a single 11-mg intravenous dose of the dihydropyridine calcium antagonist amlodipine on the coronary vascular response to the cold pressor test, a 30-s application of the dive reflex and cigarette smoking (whose effects on the coronary circulation also involve the sympathetic nervous system). In 13 normotensive male patients with severe stenoses of the left anterior descending coronary artery, the cold pressor test and diving reflex increased mean arterial pressure and rate-pressure product and caused a marked and significant rise in coronary vascular resistance (+ 12.1 +/- 4.8% and +30.4 +/- 6.8%, respectively). Mean arterial pressure, rate-pressure product, and coronary vascular resistance also increased markedly during smoking. Amlodipine caused a reduction in baseline mean arterial pressure, an increase in baseline coronary blood flow, and a marked fall in baseline coronary vascular resistance (-19.2 +/- 3.1%; p < 0.01). The coronary vascular responses to the cold pressor test and the diving reflex were unchanged with amlodipine. However, the smoking-induced increase in coronary vascular resistance was significantly attenuated after amlodipine (+3.2 +/- 2.7% vs. +16.8 +/- 7.2%; p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)