Both D- and L-arginine increase contractions to dexmedetomidine in the presence of L-name in the rat aorta with endothelium

Focused Conference Group: P15 – Endotheliumin Health and Disease. Paper No. 2194Dexmedetomidine is an anesthetic agent which can cause relaxation (due to the release of NO) and contraction (due to activation of α1 and α2 adreneoceptors) of isolated arteries. The present study investigated whether or not L-arginine or D-arginine affected the balance between relaxation and contraction in response to dexmedetomidine. Thoracic aortae with endothelium were isolated from male Sprague Dawley rats (10 week old), and suspended in organ chambers for isometric tension recording. Cumulative concentrations of dexmedetomidine were added to quiescent aortic rings, incubated with L-NAME (NOS inhibitor) and/or L-arginine or D-arginine for 40 minutes. Dexmedetomidine caused concentration-dependent contractions in the presence of L-NAME (EMax (% of 60 mM KCl): 48.20 ± 5.49, logEC50: -6.61 ± 0.18) which were potentiated significantly by both L-arginine (EMax: 81.76 ± 4.42, logEC50: -6.68 ± 0.09, P < 0.05) or D-arginine (EMax: 127.4 ± 3.55, logEC50: -6.90 ± 0.05, P < 0.05). These potentiations were reversed by (S)-(2-boronoethyl)-L-cysteine (BEC, arginase inhibitor). No such potentiation was observed in preparations without endothelium or during contractions to α1-adrenergic agonists. To conclude, both L-arginine and Darginine potentiate α2-mediated contractions by dexmedetomidine in endothelium intact rat aortae. This potentiation likely involves a product of arginase.The 16th World Congress on Basic and Clinical Pharmacology (WorldPharma2010), Copenhagen, Denmark, 17-23 July 2010. In Basic & Clinical Pharmacology & Toxicology, 2010, v. 107, suppl. 1, p. 65