Medicine & Science in Sports & Exercise:
Nitric Oxide: Role in Combating Disease
1Dept. of Med. Phys. and Cardiovasc. Res. Ctr, TAMUS HSC, College Station, TX
Our lab and others have demonstrated that experimental coronary disease established with chronic coronary occlusion (CCO) is punctuated by impaired agonist-stimulated dilation in porcine coronary vasculature.
We hypothesized that nitric oxide (NO)-mediated vasodilation responses to bradykinin (BK) and vascular endothelial growth factor-165 (VEGF) are compromised by CCO; furthermore, vascular impairment is improved by exercise training (EX).
The proximal left circumflex coronary artery (LCx) of female Yucatan mini-swine was surgically instrumented with an ameroid occluder to induce CCO and collateral development; 8 wks post-surgery animals were randomized into sedentary(SED) or EX(treadmill; 5dys/wk) protocols for 14 wks. Coronary arterioles (< 150μm) and arteries (> 500μm) were isolated from collateral-dependent (LCx) and non-occluded (left anterior descending;LAD)-perfused myocardium of SED and EX animals.
Coronary arteries exposed to CCO did not demonstrate impaired responses to BK; however, EX significantly enhanced BK-stimulated relaxation of both LAD and LCx arteries. In contrast, vasodilation responses to BK in LCx arterioles were significantly diminished in association with reduction in NO synthase (NOS) mRNA; impairments were reversed by EX. Responses to VEGF also differentiated by vessel size. LAD and LCx arteries from SED and EX animals responded similarly to VEGF. Interestingly, EX markedly enhanced VEGF-induced vasodilation of LCx arterioles. Furthermore, vasodilation of EX LCx arterioles exceeded that of EX or SED LAD arterioles in response to VEGF. Enhanced responses of LCx arterioles due to EX was abolished by inhibition of NOS and tyrosine kinase activity. This EX-induced enhanced vasodilation was not demonstrated by use of other isoforms of VEGF and required the activation of a non-tyrosine kinase VEGF receptor, neuropilin-1.
These data indicate that EX enhances endothelial-dependent, NO-mediated responses in coronary arteries and arterioles from hearts exposed to CCO, potentially via multiple mechanisms and pathways.