ENDOTHELIUM-DEPENDENT RELAXATION AND HYPERPOLARIZATION EVOKED BY BRADYKININ IN CANINE CORONARY-ARTERIES - ENHANCEMENT BY EXERCISE-TRAINING

1 Kinins, which are produced locally in arterial walls, stimulate the release of endothelium-derived vasodilator substances. Therefore, they may participate in the metabolic adaptation to chronic exercise that occurs in the coronary circulation. Experiments were designed to compa re the reactivity to bradykinin in coronary arteries isolated from sed entary and exercised-trained dogs (for 8-10 weeks). 2 The organ chambe rs used in this study were designed for measurement of isometric tensi on and cell membrane potential with glass microelectrodes. Rings of ca nine isolated coronary arteries with endothelium were suspended in the organ chambers filled with modified Krebs-Ringer bicarbonate solution (37 degrees C, gassed with 5% CO2 in 95 O-2), and were all treated wi th indomethacin to prevent interference from prostaglandins. 3 Bradyki nin evoked concentration-dependent relaxations of the coronary arterie s. However, the kinin was significantly less potent in relaxing corona ry arteries from the sedentary dogs than those from the trained ones. 4 In the presence of N-G-nitro-L-arginine (an inhibitor of nitric oxid e synthases), concentration-relaxation curves to bradykinin were shift ed to the right in both types of preparations. Nonetheless, the peptid e was still significantly more potent in arteries from exercise-traine d animals. 5 In the electrophysiological experiments, concentration-hy perpolarization curves to bradykinin obtained in arteries from sedenta ry dogs were also significantly to the right of those in vessels from exercise-trained animals. Thus, in arteries from exercised animals, br adykinin more potently evoked the release of both nitric oxide (NO) an d endothelium-derived hyperpolarizing factor (EDHF). 7 The angiotensin converting enzyme (ACE)-inhibitor, perindoprilat, shifted to the left the concentration-relaxation curves to bradykinin obtained under cont rol conditions and in the presence of N-G-nitro-L-arginine. The concen tration-hyperpolarization curves to bradykinin were also shifted to th e left by perindoprilat. The shift induced by the ACE-inhibitor in eit her type of preparation was not significantly different. 8 These findi ngs demonstrate that exercise-training augments the sensitivity of the coronary artery of the dog to the endothelium-dependent effects of br adykinin. This sensitization to bradykinin may reflect an increased ro le of both NO and EDHF, and is not the consequence of differences in A CE activity in the receptor compartment.