URIDINE ADENOSINE TETRAPHOSPHATE‐INDUCED CONTRACTION IS MODULATED BY THE ENDOTHELIUM AND INVOLVES AN INCREASED SUPEROXIDE FORMATION IN DOCA‐SALT HYPERTENSION

Abstract

The uridine adenosine tetraphosphate (Up4A), a dinucleotide that contains both purine and pirimidine moieties, described as a novel potent nonpeptidic vasoconstrictor has been shown to be released from the endothelium upon chemical and mechanical stimulation, suggesting a potential role as an endothelium-derived contracting factor (EDCF). There have been strong evidences that EDCF are actually increased in hypertension. We hypothesize that the contraction induced by Up4A is increased in aortic rings from DOCA-salt hypertensive rats due to an endothelium dysfunction and/or changes in the mechanisms of vasoconstriction. Aorta rings were isolated from 30 days DOCA hypertensive (n=5) or sham-operated (n=5) rats, for isometric tension recordings. Concentration-effect curves to Up4A (10-11 to 10-5M) were performed in aortic rings in the presence and in the absence of the endothelium. Concentration-effect curves to tempol (2.5X10-3 to 1.5x10-2M) were performed in endothelium denuded aortic rings pre-contracted with Up4A (10-5M). The contraction to Up4A was greater in vessels from DOCA rats. Endothelium removal potentiated the contractile response to Up4A. The relaxation induced by tempol in endothelium denuded aortic rings pre-contracted with Up4A was potentiated in rings from DOCA when compared to sham-operated rats. The contraction induced by Up4A is modulated by the endothelium and the involvement of superoxide anion seems to be significantly increased on endothelium denuded aortic rings from DOCA-salt hypertensive rats. These data suggest that the functional endothelium is a key modulator of the effect of the putative EDCF Up4A and that its effect involves an increased superoxide formation in DOCA hypertension. NIH (P01 HL074167)