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

ECU Author/Contributor (non-ECU co-authors, if there are any, appear on document)

Mohammed Fahim (Creator)

Syed Jamal Mustafa (Creator)

Institution

East Carolina University (ECU )

Web Site: http://www.ecu.edu/lib/

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: GS 216804CAD4R-PIA4CPA4ENBA. 5 Removal of endothelium abolished the adenosine analogue induced contractions in SHR aorta nd attenuated the vasorelaxation responses in the WKY and SHR. 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 ctivity 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

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Other

British Journal of Pharmacology. 134:8(December 2001) p. 1760-1766.

Language: English

Date: 2011

Keywords

A1 adenosine receptor, A2 adenosine receptor, vascular endothelium, vascular smooth muscle, indomethacin, free radicals

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