title: Role of endothelium in adenosine receptor-mediated vasorelaxation in hypertensive rats.
abstract: The present study was designed to investigate the role of endothelium derived relaxing factor nitric oxide (NO) in adenosine A2 receptor mediated vasorelaxation in normotensive (WKY) and hypertensive (SHR) rat aortic ring preparations. Adenosine analogues, 2-chloroadenosine (CAD) and 5-ethylcarboxamidoadenosine (NECA) produced concentration-dependent (10(-9)-10(-4) M) relaxation in phenylephrine (1 x 10(-6) M) precontracted vascular rings, which was significantly shifted to the right in SHR compared to WKY rats. Endothelium removal attenuated CAD and NECA relaxation responses in both SHR and WKY and abolished the difference in relaxation between SHR and WKY vascular tissues. The relaxation response to CAD was antagonised by adenosine A2 receptor antagonist, 8-sulfophenyltheophylline (8-SPT, 50 x 10(-6) M). The antagonism by 8-SPT was lower in SHR as compared to WKY tissues. L-monomethylarginine (L-LMMA) (30 x 10(-6) M) significantly shifted the CAD relaxation to the right, which was reversed by the addition of L-arginine (100 x 10(-6) M) in both SHR and WKY rats. However, the rightward shift by L-NMMA was smaller in SHR compared to WKY vascular tissues. Vasorelaxation response to acetylcholine (1 x 10(-6) M) was significantly inhibited (50%) in SHR rings compared to WKY. The relaxation produced by sodium nitroprusside (10(-9)-10(-5) M) in endothelium-intact and -denuded aortic rings showed no difference between SHR and WKY. Isoproterenol produced concentration-dependent (10-9-10-5 M) relaxation, which was shifted to the right in SHR compared to WKY rings with an intact endothelium, while the removal of endothelium abolished the difference in the response between SHR and WKY. The results suggest: (i) adenosine A2 receptors mediate vasorelaxation in part through endothelium possibly by releasing nitric oxide (NO); (ii) the impairment of endothelium may be one of the factors for the attenuation of adenosine receptor and receptor-mediated responses in SHR.
authors.affiliation: Department of Pharmacology, School of Medicine, East Carolina University, Greenville, NC 27858, USA. vpci@delnet.ren.nic.in
authors.forename: M
authors.initials: M
authors.lastname: Fahim
authors.forename: T
authors.initials: T
authors.lastname: Hussain
authors.forename: S J
authors.initials: SJ
authors.lastname: Mustafa
mesh_terms: D000241:Adenosine / Q000032:analysis / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000502:physiology*; D006973:Hypertension / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D009569:Nitric Oxide / Q000502:physiology; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D018047:Receptors, Purinergic P1 / Q000502:physiology*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1; D014665:Vasodilator Agents; D009569:Nitric Oxide; D000241:Adenosine