Effect of some products of protein catabolism on the endothelium- dependent and -independent relaxation of rabbit thoracic aorta rings

R Sorrentino, L Sorrentino and A Pinto

Department of Experimental Pharmacology, University of Naples Federico II, Italy.

We have investigated the effect that some products of protein catabolism have on endothelium-dependent and -independent relaxation of rabbit aorta rings precontracted with phenylephrine (PE). All the products tested, i.e., creatinine (CRT), guanidinosuccinic acid (GSA), urea (UR), guanidine (GND) and methylguanidine (MG), are structurally related to L-arginine (L-ARG), the substrate for nitric oxide (NO) biosynthesis which accounts for the biological properties of endothelium-derived relaxing factor (EDRF). Endothelium-derived NO (EDNO) release was induced by agents acting via a receptor- [acetylcholine (ACh)] or a nonreceptor-mediated mechanism (calcium ionophore A23187), and the endothelial-independent relaxation was induced by the NO donor glyceryl trinitrate (GTN). CRT (0.1-10 mM) did not modify the endothelium-dependent relaxation caused by ACh or A23187 but produced a small increase in the response to the endothelium- independent vasorelaxant GTN. Concentrations of GSA up to 1 mM did not affect the relaxation of rabbit aortic rings induced by either ACh or A23187, but at 10 mM, GSA enhanced the relaxation produced by these agents. UR (1-100 mM) inhibited, in a concentration-dependent manner, the relaxation induced by ACh, but not that caused by A23187 or GTN. By comparison, GND and MG (0.1-10 mM) produced a concentration-related inhibition of both ACh- and A23187-induced relaxation. The inhibition by these compounds was either completely or partially reversed by L- ARG. In contrast, the relaxation induced by GTN was inhibited only by higher concentrations (10 mM) of GND or MG. These results indicate that some products of protein catabolism can reduce EDNO formation in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)

Volume 266, Issue 2, pp. 626-633, 08/01/1993
Copyright © 1993 by American Society for Pharmacology and Experimental Therapeutics

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