Effect of l-arginine on endothelium-dependent coronary vasodilatory reserve in spontaneously hypertensive rats

Abstract

Background Hypertensive heart disease usually involves impairment of the coronary circulation, with or without coronary artery stenosis. Nitric oxide (NO) controls coronary vascular tone, and it has been demonstrated that NO release is impaired in hypertension. Therefore, NO may contribute to impaired coronary circulation in the hypertensive heart. Objective The aim of this study was to determine whether vasodilatory reserve is decreased by reduction of NO release in the coronary arteries of the hypertensive heart and whether chronic administration of l-arginine can improve this decreased reserve and coronary vascular resistance. Methods Nine-week-old spontaneously hypertensive rats (SHR) and age-matched Wistar-Kyoto rats (WKY) were employed in this study. l-arginine was administered to half of the SHR for 3 weeks. Isolated heart was perfused with modified Krebs-Henselite buffer in a Langendorff apparatus. Perfusion pressure and flow obtained by perfusing isolated hearts were measured, after which coronary perfusion resistance (CPR) was calculated. Minimal coronary perfusion resistance (MCPR) was obtained using adenosine infusion. Results: MCPR was significantly higher in SHR (n = 12) than in WKY (n = 6) (mean ± SEM, 0.116 ± 0.013 vs 0.041 ± 0.009 mm Hg/mL per min/100 g, respectively; P < 0.001). Infusion of l Gmonomethyl- l-arginine ( l-NMMA) elicited an increase in CPR in WKY but not in SHR (66.3% ± 12.4% vs 9.5% ± 2.6%, respectively; P < 0.05). Administration of l-arginine in SHR did not alter the development of hypertension or cardiac hypertrophy. However, in response to infusion of l-NMMA, CPR was restored (9.5% ± 2.6% vs 60.4% ± 7.0%, respectively; P < 0.05) and MCPR was decreased (0.116 ± 0.013 vs 0.085 ± 0.003 mm Hg/mL per min/100 g, respectively; P < 0.05) in untreated versus treated SHR. Conclusions The findings suggest that l-arginine restores the diminished vasoconstrictive response to l-NMMA infusion and the increased MCPR in the coronary vessels of SHR. l-arginine appears to improve impaired endothelium-dependent coronary vasodilatory reserve in SHR without lowering blood pressure.