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 compare the reactivity to bradykinin in coronary arteries isolated from sedentary and exercised-trained dogs (for 8-10 weeks). 2. The organ chambers used in this study were designed for measurement of isometric tension and cell membrane potential with glass microelectrodes. Rings of canine 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 O2), and were all treated with indomethacin to prevent interference from prostaglandins. 3. Bradykinin evoked concentration-dependent relaxations of the coronary arteries. However, the kinin was significantly less potent in relaxing coronary arteries from the sedentary dogs than those from the trained ones. 4. In the presence of NG-nitro-L-arginine (an inhibitor of nitric oxide synthases), concentration-relaxation curves to bradykinin were shifted to the right in both types of preparations. Nonetheless, the peptide was still significantly more potent in arteries from exercise-trained animals. 5. In the electrophysiological experiments, concentration-hyperpolarization curves to bradykinin obtained in arteries from sedentary dogs were also significantly to the right of those in vessels from exercise-trained animals. Thus, in arteries from exercised animals, bradykinin more potently evoked the release of both nitric oxide (NO) and 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 control conditions and in the presence of NG-nitro-L-arginine. The concentration-hyperpolarization curves to bradykinin were also shifted to the left by perindoprilat. The shift induced by the ACE-inhibitor in either type of preparation was not significantly different. 8. These findings demonstrate that exercise-training augments the sensitivity of the coronary artery of the dog to the endothelium-dependent effects of bradykinin. This sensitization to bradykinin may reflect an increased role of both NO and EDHF, and is not the consequence of differences in ACE activity in the receptor compartment.
Mombouli
J V
JV
Center for Experimental Therapeutics, Baylor College of Medicine, Houston, Texas 77030, U.S.A.
Nakashima
M
M
Hamra
M
M
Vanhoutte
P M
PM
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology; D006224:Cricetinae; D015237:Dinoprost / Q000494:pharmacology; D004285:Dogs; D004594:Electrophysiology; D004730:Endothelium, Vascular / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D010805:Physical Conditioning, Animal
D000806:Angiotensin-Converting Enzyme Inhibitors; D004791:Enzyme Inhibitors; D019335:Nitroarginine; D015237:Dinoprost; D019001:Nitric Oxide Synthase; D001920:Bradykinin