Exercise Training Restores Coronary Arteriolar Dilation to NOS Activation Distal to Coronary Artery Occlusion

Abstract

Objective-Exercise training has been shown to restore vasodilation to nitric oxide synthase (NOS) activation in arterioles distal to coronary artery occlusion. Because reactive oxygen species are generated during NOS uncoupling and the production of vasodilator H 2 O 2 is increased during exercise in patients with coronary disease, we proposed that H 2 O 2 may contribute to the restoration of vasodilation in porcine coronary occlusion model. Methods and Results-Left circumflex (LCX) coronary artery of miniature swine was progressively occluded for 8 weeks followed by exercise training (EX; 5 days/wk treadmill) or sedentary (SED) protocols for 12 weeks. Arterioles were isolated from distal LCX and nonoccluded left anterior descending (LAD) artery for in vitro study. Vasodilation to NOS activators adenosine and ionomycin was impaired in SED LCX, but not LAD, arterioles. This impairment was restored by L-arginine. NO production induced by adenosine was also reduced in SED LCX arterioles. EX had no effect on LAD arterioles but improved NO production and restored dilation of LCX arterioles. NOS blockade (L-NAME) inhibited vasodilation to NOS activators in LAD (SED & EX) arterioles but was ineffective in SED LCX arterioles. In EX LCX arterioles, vasodilation to NOS activators was slightly inhibited by L-NAME but abolished by catalase. H 2 O 2 production was markedly increased by adenosine in EX LCX arterioles. Conclusions-This study demonstrates that endothelium-dependent NO-mediated dilation is impaired in SED LCXarterioles and that EX training restores the impaired function. It appears that H 2 O 2 , in addition to NO, contributes significantly to EX-induced restoration of endothelium-dependent dilation of coronary arterioles distal to occlusion.

Selective Activation of Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1 Mediates C-Reactive Protein–Evoked Endothelial Vasodilator Dysfunction in Coronary Arterioles

“…However, this modified catalase caused loss of basal tone of coronary arterioles, and the vasomotor activity could not be further studied. Nevertheless, using an effective concentration of unmodified catalase, 29,30 we found that the adverse effect of CRP remained (Online Figure II), suggesting nominal contribution of hydrogen peroxide in mediating the CRP effect in our preparation.…”

“…The roles of LOX-1 and CD32 in mediating the CRP effect were examined in a separate group of vessels by determining dilation to serotonin before and after coadministration of CRP with an anti-LOX-1 antibody (5 µg/mL; Abcam) 25 or an anti-CD32 antibody (5 µg/mL; Santa Cruz Biotechnology). 26,27 κ-Carrageenan (125 µg/mL), a LOX-1 antagonist, 25,28 and catalase (1000 U/mL), 29,30 the hydrogen peroxide scavenger, were administered to determine the role of LOX-1 and hydrogen peroxide, respectively, in the observed CRP effect. In another cohort of vessels, vasodilation to arachidonic acid (10 µmol/L), 10 an endothelium-dependent PGI 2 -mediated agonist, was examined before and after incubation with PGI 2 synthase inhibitor trans-2-phenyl cyclopropylamine (TPC; 100 µmol/L) 10 or after 60-minute intraluminal incubation with recombinant CRP (7 µg/mL) in the absence or presence of an anti-LOX-1 antibody (5 µg/ mL), TPC plus an anti-LOX-1 antibody, or an anti-CD32 antibody (5 µg/mL).…”

Improved arterial flow-mediated dilation after exertion involves hydrogen peroxide in overweight and obese adults following aerobic exercise training

“…Animal models have also found that regular aerobic exercise restore arterial function in the microcirculation in an H 2 O 2 -dependent fashion. In a porcine model of coronary artery disease, regular exercise restored microvessel dilatory function via H 2 O 2 -mediated dilation [29]. Huang et al [30] showed impaired microvessel FMD following transient high intraluminal pressure (140 mmHg) was restored following administration of exogenous SOD, also suggesting a role H 2 O 2 -mediated FMD.…”

Histamine-Induced Dilation of Isolated Porcine Retinal Arterioles: Role of Endothelium-Derived Hyperpolarizing Factor

“…Since H 2 O 2 and the CYP enzyme metabolites EETs have been suggested to be involved in the EDHF-induced vasodilation in some vascular beds, 9 we tested this possibility by pretreating the vessels with the effective concentration of H 2 O 2 scavenger catalase (1000 U/mL) 40,41 and the CYP2C9 enzyme inhibitor sulfaphenazole (10 lM), 42 respectively. The role of gap junctions in histamine-induced responses was tested by the gap junction inhibitor carbenoxolone (100 lM).…”