EFFECTS OF AMLODIPINE ON CORONARY HEMODYNAMICS AND VASCULAR-RESPONSESTO SYMPATHETIC-STIMULATION IN PATIENTS WITH CORONARY HEART-DISEASE

Dihydropyridines (DHPs) exert a powerful coronary vasodilator action, but whether they actually affect the coronary vasomotor effects elicit ed by an increase in cardiac sympathetic drive is controversial. We as sessed the effects of the DHP calcium antagonist amlodipine on coronar y hemodynamics and vascular response to sympathetic activation in pati ents with coronary heart disease. In the control condition, mean arter ial pressure (MAP, aortic catheter), heart rate (HR, ECG), rate-pressu re product (RPP), coronary sinus blood flow (CBF, thermodilution) and coronary vascular resistance (CVR) ratio between MAP and CBF) were mea sured in all our case series (13 patients with angiographically docume nted severe coronary artery disease) before and during a 2-min cold pr essor test (CPT) and a 30-s diving (D) and, in the 8 patients of this case series who were smokers, also before and during smoking a cigaret te (S, nicotine content 1.0 mg for 10 min). The same protocol used in control condition was repeated 30 min after intravenous (i.v.) bolus a dministration of 11 mg amlodipine. CPT, diving, and smoking increased MAP and RPP and caused a marked and significant increase in CVR (+ 12. 1 +/- 4.8, +30.4 +/- 6.8, and + 16.8 +/- 7.2%, respectively). Amlodipi ne reduced MAP, increased CBF, and caused a marked decrease in CBF. Th e drug did not modify responses to CPT and diving or pressure and HR r esponses to smoking, whereas the smoking-induced increase in coronary vascular resistance was attenuated after amlodipine administration (3.2 +/- 2.7%, p<0.05 vs. control condition). Thus, amlodipine does not attenuate the sympathetic coronary vasoconstrictor effects of CPT and diving. However, owing to marked reduction in baseline coronary vasom otor tone, sympathetic stimuli elicit less peak coronary vasoconstrict ion after administration than before administration of amlodipine. The drug also attenuates coronary vasoconstriction to smoking, presumably because this stimulus is not entirely sympathetic.