Vasodilator responses to adenosine and hyperemia are mediated by A(1) and A(2) receptors in the cat vascular bed.
Hemodynamic responses to adenosine, the A(1) receptor agonists N(6)-cyclopentyladenosine (CPA) and adenosine amine congener (ADAC), and the A(2) receptor agonist 5'-(N-cyclopropyl)-carboxamido-adenosine (CPCA) were investigated in the hindquarter vascular bed of the cat under constant-flow conditions. Injections of adenosine, CPA, ADAC, CPCA, ATP, and adenosine 5'-O-(3-thiotriphosphate) (ATPgamma S) into the perfusion circuit induced dose-related decreases in perfusion pressure. Vasodilator responses to the A(1) agonists were reduced by the A(1) receptor antagonists KW-3902 and CGS-15943, whereas responses to CPCA were reduced by the A(2) antagonist KF-17837. Vasodilator responses to adenosine were reduced by KW-3902, CGS-15943, and by KF-17837, suggesting a role for both A(1) and A(2) receptors. Vasodilator responses to ATP and the nonhydrolyzable ATP analog ATP gamma S were not attenuated by CGS-15943 or KF-17837. After treatment with the nitric oxide synthase inhibitor N(omega)-nitro-L-arginine methyl ester, the cyclooxygenase inhibitor sodium meclofenamate, or the ATP-dependent K(+) (K) channel antagonists U-37883A or glibenclamide, responses to adenosine and ATP were not altered. Responses to adenosine, CPA, and CPCA were increased in duration by rolipram, a type 4 cAMP phosphodiesterase inhibitor, but were not altered by zaprinast, a type 5 cGMP phosphodiesterase inhibitor. When blood flow was interrupted for a 30-s period, the magnitude and duration of the reactive vasodilator response were reduced by A(1) and A(2) receptor antagonists. These data suggest that vasodilator responses to adenosine and the A(1) and A(2) agonists studied are not dependent on the release of cyclooxygenase products, nitric oxide, or the opening of K channels in the regional vascular bed of the cat. The present data suggest a role for cAMP in mediating responses to adenosine and suggest that vasodilator responses to adenosine and to reactive hyperemia are mediated in part by A(1) and A(2) receptors in the hindquarter vascular bed of the cat.
Bivalacqua
Trinity J
TJ
Department of Pharmacology, Tulane University Health Sciences Center, New Orleans, Louisiana 70112, USA.
Champion
Hunter C
HC
Lambert
David G
DG
Kadowitz
Philip J
PJ
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D002415:Cats; D004305:Dose-Response Relationship, Drug; D005260:Female; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D006614:Hindlimb / Q000098:blood supply*; D006940:Hyperemia / Q000378:metabolism*; D008297:Male; D010477:Perfusion; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D011799:Quinazolines / Q000494:pharmacology; D018047:Receptors, Purinergic P1 / Q000378:metabolism*; D014230:Triazoles / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D014970:Xanthines / Q000494:pharmacology
D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D011799:Quinazolines; D018047:Receptors, Purinergic P1; D014230:Triazoles; D014970:Xanthines; C081198:KF 17837; C022571:adenosine 5'-O-(3-thiotriphosphate); C048599:N(6)-cyclopentyladenosine; C024311:N-cyclopropyl adenosine-5'-carboxamide; C073525:rolofylline; D000255:Adenosine Triphosphate; C106045:adenosine amine congener; D000241:Adenosine; C052410:9-chloro-2-(2-furyl)-(1,2,4)triazolo(1,5-c)quinazolin-5-imine