Reactivity of isolated porcine coronary resistance arteries to cholinergic and adrenergic drugs and transmural pressure changes

Abstract

The reactivity of porcine intramyocardial resistance arteries (223 ± 7 μm i.d., n=30) was investigated with a pressurized in vitro preparation. Diameter changes in response to acetylcholine and to adrenergic drugs and dynamic changes in transmural pressure changes were investigated. Acetylcholine produced concentration-dependent constrictions, causing maximal reductions of 71 ± 3% in lumen diameter, with EC50 values averaging 1.9 x 10-7 M (n = 7). These responses were inhibited by atropine (10-7 M) and therefore were mediated by muscarinic receptors. In addition, acetylcholine did not elicit relaxation in nine out of 10 vessels precontracted with U46619 (10-7 M). Norepinephrine and epinephrine never produced constrictions (n = 6) even in the presence of propranolol (10-6 M). Both norepinephrine and isoproterenol caused dose-dependent relaxations in acetylcholine-precontracted vessels, with IC50 values of 8.2 x 10-7 M (n = 5) and 6.6 x 10-8 M (n = 6), respectively. These relaxations were suppressed by propranolol. Between transmural pressures of 10 and 90 mm Hg, there was no intrinsic myogenic tone (n = 7). In addition, the vessels responded only passively to sudden pressure changes of 40 mm Hg. In all vessels, the functional integrity of the endothelium was verified by relaxations to substance P (10-8 M) and/or bradykinin (10-8 M). This is the first in vitro study of coronary resistance arteries that demonstrates that 1) acetylcholine is a potent constrictor of these arteries, suggesting that parasympathetic mechanisms may play an important role in coronary blood flow regulation; 2) α-adrenoreceptor influence is minimal or entirely absent; and 3) these arteries do not possess an intrinsic myogenic tone and respond passively to transmural pressure change. Hence, myogenic mechanisms do not appear to be of primary importance in the autoregulation of coronary blood flow.