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

Background: Hypertensive heart disease usually involves impairment of the c oronary 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 impai red coronary circulation in the hypertensive heart. Objective: The aim of this study was to determine whether vasodilatory rese rve is decreased by reduction of NO release in the coronary arteries of the hypertensive heart and whether chronic administration of L-arginine can im prove this decreased reserve and coronary vascular resistance. Methods: Nine-week-old spontaneously hypertensive rats (SHR) and age-matche d mistar-Kyoto rats (WKY) were employed in this study. L-arginine was admin istered to half of the SHR for 3 weeks. Isolated heart was perfused with mo dified Krebs-Henselite buffer in a Langendorff apparatus. Perfusion pressur e and flow obtained by perfusing isolated hearts were measured, after which coronary perfusion resistance (CPR) was calculated. Minimal coronary perfu sion 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, r espectively; P < 0.001). Infusion of L(G)monomethyl-L-arginine (L-NMMA) eli cited 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 untreate d versus treated SHR. Conclusions: The findings suggest that L-arginine restores the diminished v asoconstrictive response to L-NR IMA infusion and the increased MCPR in the coronary vessels of SHR. L-arginine appears to improve impaired endotheliu m-dependent coronary vasodilatory reserve in SHR without lowering blood pre ssure.