Endothelium-Mediated Relaxation of Porcine Collateral-Dependent Arterioles Is Improved by Exercise Training

Abstract

Background-Endothelium-dependent modulation of coronary tone is impaired in the collateral-dependent coronary microcirculation. We used a porcine model of chronic coronary occlusion and collateral development to evaluate the hypothesis that exercise training enhances endothelium-mediated relaxation and increases endothelial nitric oxide synthase (ecNOS) mRNA levels of collateral-dependent microvasculature. Methods and Results-Adult female miniature swine were subjected to chronic, progressive ameroid occlusion of the proximal left circumflex coronary artery (LCx); after 2 months, animals were randomly exposed to 16-week exercise-training (EX group; treadmill running) or sedentary (SED group; cage confinement) protocols. After completion of EX or SED programs, coronary arterioles (Ϸ100 m in diameter) were isolated from collateral-dependent LCx (distal to occlusion) and nonoccluded left anterior descending coronary artery (LAD) regions of each heart. Arterioles were studied by in vitro videomicroscopy or frozen for ecNOS mRNA analysis (RT-PCR techniques). Relaxation to the endothelium-dependent vasodilator bradykinin was decreased (PϽ0.05) in arterioles isolated from collateral-dependent LCx versus nonoccluded LAD regions of SED animals. Bradykinin-mediated relaxation, however, was not different in LCx versus LAD arterioles isolated from EX animals. Nitroprusside-induced relaxation was unaffected by either chronic occlusion or exercise. Importantly, ecNOS mRNA expression was significantly decreased in arterioles isolated from LCx versus LAD regions of SED animals. After training, ecNOS mRNA expression was not different between LAD and LCx arterioles. Conclusions-These data indicate that exercise training enhances bradykinin-mediated relaxation of collateral-dependent LCx arterioles isolated after chronic coronary occlusion, most likely because of effects on ecNOS mRNA expression and increased production of NO.

Propolis and swimming in the prevention of atherogenesis and left ventricular hypertrophy in hypercholesterolemic mice

“…Studies have shown that regular physical activity promotes the reduction of the inactivation of nitric oxide (Fogarty et al, 2004;Traverse et al, 2000), increases the production of nitric oxide (Takamura et al, 2002), increases the expression of endothelial nitric oxide synthase (eNOS) (Griffin et al, 2001) and promotes angiogenesis induced by vascular endothelial growth factor, and, with the net effect of increasing the bioavailability of nitric oxide.…”

Exercise Training Enhances Vasodilation Responses to Vascular Endothelial Growth Factor in Porcine Coronary Arterioles Exposed to Chronic Coronary Occlusion

“…6 Furthermore, a significant body of evidence indicates that impaired endothelial function and altered vasomotor responsiveness of collateral-dependent vasculature contribute to abnormal regulation of coronary tone distal to CCO. [7][8][9][10] For instance, impaired endothelium-dependent nitric oxide (NO)-mediated vasodilation persists in the microvasculature distal to the occlusion 7,8,10 and is associated with CCO-induced reduction in endothelial cell NO synthase (ecNOS) mRNA in coronary arterioles. 10 Because NO plays pivotal roles in key endothelial signaling pathways, altered NO-dependent functions may have important consequences on vasomotor and angiogenic responses in the diseased heart.…”

Effects of exercise training on the vascular reactivity of the whole kidney circulation in rabbits

“…Endothelium dysfunction, which can be evidenced by an impairment in endothelium-dependent relaxation, plays a pivotal role in the pathogenesis of cardiovascular diseases, such as arterial hypertension and coronary heart disease (54), as well as in diabetic angiopathy (13). Moreover, NO interferes with key events involved in the development of atherosclerosis, such as smooth muscle cell proliferation, platelet adhesion and vessel wall interaction, and monocyte and leucocyte adhesion (54).Several studies demonstrated that chronic aerobic exercise alters endothelial function, improving vasodilating mechanisms mediated by NO (15,38,59), EDHF (33,36), and prostanoid metabolites (21), mainly in resistance vessels of the cardiac and skeletal muscle vascular beds (36,47). It is suggested that increased vascular wall shear stress associated with acute bouts of aerobic exercise may represent the main stimulus for vascular adaptations induced by chronic aerobic exercise (3,39,41).…”

“…Several studies demonstrated that chronic aerobic exercise alters endothelial function, improving vasodilating mechanisms mediated by NO (15,38,59), EDHF (33,36), and prostanoid metabolites (21), mainly in resistance vessels of the cardiac and skeletal muscle vascular beds (36,47). It is suggested that increased vascular wall shear stress associated with acute bouts of aerobic exercise may represent the main stimulus for vascular adaptations induced by chronic aerobic exercise (3,39,41).…”