Evidence for the presence of A(1) adenosine receptors in the aorta of spontaneously hypertensive rats.
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 effects of various adenosine analogues. 2. In phenylephrine contracted aortic rings, concentration-response curves were constructed by cumulative additions (10(-11) - 10(-5) M) of (2S)-N(6)-[2-endo-Norbornyl] adenosine (ENBA), N(6)-cyclopentyladenosine (CPA), R-N(6)-(2-phenylisopropyl) adenosine (R-PIA), 2-p-(-2-carboxyethyl) phenethylamino-5'-N-thylcarboxamido adenosine (CGS-21680). 3. A non-specific adenosine receptor agonist 2-chloroadenosine (CAD) resulted in biphasic response with a small contraction at lower concentrations (10(-9) - 10(-8) M) followed by a significant relaxation at higher concentration in endothelium-intact SHR tissues, suggesting presence of both A(1) and A(2) adenosine receptors in SHR aorta. However, only relaxation was observed in WKY. 4. Contractile response in SHR had the following rank order of potency: ENBA>CPA>R-PIA>CAD. The relaxation response in SHR and WKY had the following rank order of potency: CGS 21680>CAD>R-PIA>CPA>ENBA. 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 A(1) adenosine receptor antagonist N(6)-endonorbornan-2-yl-9-methyladenine (N-0861). A(2) adenosine receptor antagonist, 3,7-dimethyl-1-proparglyxanthine (DMPX) did not affect the contraction response of adenosine analogues. 7. Endothelium-dependent contractions elicited by A(1) 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.
Fahim
M
M
Department of Pharmacology, School of Medicine, East Carolina University, Greenville, North Carolina, NC 27858, USA. vpciphysiology@yahoo.com
Mustafa
S J
SJ
D000225:Adenine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000503:physiopathology*; D046508:Culture Techniques; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000503:physiopathology; D016166:Free Radical Scavengers / Q000494:pharmacology; D006973:Hypertension / Q000235:genetics / Q000503:physiopathology*; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000503:physiopathology; D009636:Norbornanes / Q000494:pharmacology; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013805:Theobromine / Q000031:analogs & derivatives* / Q000494:pharmacology; D014664:Vasodilation / Q000502:physiology
D016166:Free Radical Scavengers; D009636:Norbornanes; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; C073387:N 0861; C057837:3,7-dimethyl-1-propargylxanthine; D000225:Adenine; D000241:Adenosine; D013805:Theobromine; D007213:Indomethacin