ENDOTHELIAL MODULATION OF ALPHA(1)-ADRENOCEPTOR CONTRACTILE RESPONSESIN THE TAIL ARTERY OF SPONTANEOUSLY HYPERTENSIVE RATS

1 Vascular contraction induced by phenylephrine was studied in tail ar tery rings from spontaneously hypertensive (SHR) and Wistar Kyoto rats (WKY) with particular focus on the role of endothelium. The influence of receptor reserve and the density of alpha(1)-adrenoceptors on the possible differences observed were also analysed. 2 Phenylephrine (0.0 1-100 mu M) induced concentration-dependent vasoconstrictions. The max imum response (alpha, P < 0.001) was greater but the pEC(50) (P < 0.05 ) smaller in rings from SHR than from WKY rats irrespective of the pre sence or absence of endothelium. 3 Removal of endothelial cells result ed in a decrease of the maximum contraction with no modification in th e PEC(50) in arteries from both WKY and SHR. 4 The density of alpha(1) -adrenoceptors (B-max) and the dissociation constant (K-D) were found to be the same for preparations from SHR and WKY rats in [H-3]-prazosi n binding experiments. 5 The apparent affinity (pK(A)) determined by t he nested hyperbolic method and the operational model was similar in t ail arteries from the two rat strains, irrespective of the presence or absence of endothelium. However, in endothelium-denuded rings, the pK (A) value was enhanced when compared with intact rings, in both SHR an d WKY rats. 6 In rings from hypertensive rats, the operational paramet er maximum possible effect (E(m)) was greater and the agonist efficacy (tau) was smaller than in rings from normotensive rats. When the endo thelium was removed log tau and E(m) diminished in preparations from b oth rat strains. 7 In summary, the increased maximum responsiveness to phenylephrine in rings from SHR could be due to enhancement in E(m). The log tau values indicate a deterioration in the transduction of the stimulus provided by the agonist in tail arteries from hypertensive a nimals. This study also suggests that the absence of endothelium modif ies the alpha(1)-adrenoceptor-mediated vasocontriction probably by alt ering the transduction signalling mechanisms. The importance of analys ing the degree of endothelium functionality when comparing results fro m different groups of rats is stated.