Evidence for the presence of A1 adenosine receptors in the aorta of spontaneously hypertensive rats

Abstract

1 Isolated aortic rings (endothelium-intact and -denuded) from spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats were used in this study to examine the vasoactive e ects of various adenosine analogues. 2 In phenylephrine contracted aortic rings, concentration-response curves were constructed by cumulative additions (10711 ±1075 M) of (2S)-N6-[2-endo-Norbornyl] adenosine (ENBA), N6- cyclopentyladenosine (CPA), R-N6-(2-phenylisopropyl) adenosine (R-PIA), 2-p-(-2-carboxyethyl) phenethylamino-5'-N-thylcarboxamido adenosine (CGS-21680). 3 A non-speci®c adenosine receptor agonist 2-chloroadenosine (CAD) resulted in biphasic response with a small contraction at lower concentrations (1079 ±1078 M) followed by a signi®cant relaxation at higher concentration in endothelium-intact SHR tissues, suggesting presence of both A1 and A2 adenosine receptors in SHR aorta. However, only relaxation was observed in WKY. 4 Contractile response in SHR had the following rank order of potency: ENBA4CPA4R- PIA4CAD. The relaxation response in SHR and WKY had the following rank order of potency: CGS 216804CAD4R-PIA4CPA4ENBA. 5 Removal of endothelium abolished the adenosine analogue induced contractions in SHR aorta and attenuated the vasorelaxation responses in the WKY and SHR. 6 The contractile response in SHR was abolished by A1 adenosine receptor antagonist N6- endonorbornan-2-yl-9-methyladenine (N-0861). A2 adenosine receptor antagonist, 3,7-dimethyl-1-proparglyxanthine (DMPX) did not a ect the contraction response of adenosine analogues. 7 Endothelium-dependent contractions elicited by A1 receptor agonists were blocked by indomethacin and by free radical scavengers. 8 These data suggest that the contractile response to adenosine analogues in SHR aorta is probably mediated by free radicals which are generated through the increased cyclo-oxygenase activity occurring in the vascular endothelium of SHR but not the WKY rats. British Journal of Pharmacology (2001) 134, 1760 ± 1766. Originally published British Journal of Pharmacology, Vol. 134, No. 8, Dec 2001