Enhanced coronary vasodilation in isolated Langendorff‐perfused hearts of asthmatic mice

Abstract

Clinical studies have shown that asthma is associated with high risk of cardiovascular diseases. We previously demonstrated that asthmatic mice have impaired vascular reactivity and endothelial function in aorta. However, little is known regarding coronary vascular reactivity in asthmatic mice. This study aims to examine the coronary flow response to vasodilators and to short period of ischemia in isolated hearts of asthmatic mice. Asthmatic mice were induced by I.P. injection of ovalbumin (OVA, 0.2 μg) on days 1 and 6, followed by 5% OVA aerosol challenges on days 11–13. Hearts were isolated and perfused on day 14 to examine the coronary flow (CF) response. CF was measured using Langendorff system. Baseline CF was comparable between normal and sensitized mice. However, peak CF and repayment/debt ratio following a 15‐s occlusion were significantly higher (~1.14 and 1. 55 folds increase, respectively, p<0.05) in sensitized versus control mice. In lines with the enhanced reactive hyperemic response, acetylcholine (ACH, 10−9‐105.5M) induced an augmented flow increase (Emax=2.8 ± 0.16 and 2.4 ± 0.14 times the baseline in sensitized versus control mice, respectively, p<0.05) which was not affected by L‐NAME (nitric oxide synthase inhibitor). Additionally, sodium nitroprusside (SNP, 10−5 M) induced a ~25% more coronary flow increase (p<0.05) in sensitized mice. Our data suggest that during early stage of sensitized asthmatic mouse model, the coronary circulation demonstrates an enhanced flow reserve though the baseline flow is unchanged. The changes in coronary flow reserve in asthmatic mice indicate one of the potential protective mechanisms against hypoxia/ischemia–induced heart injury in asthmatic patients. Supported by HL 027339 (SJM) and WVCTSI Pilot Grant NIH/NIGMS U54GM104942 (DSP)