Interactions of adenosine A1 receptor-mediated renal vasoconstriction with endogenous nitric oxide and ANG II.
Renal vasoconstrictor responses to the adenosine A1 agonist N6-cyclopentyladenosine (CPA) were compared in the in situ autoperfused rat kidney to responses evoked by angiotensin II (ANG II), endothelin-1 (ET-1), arginine vasopressin (AVP), carbocyclic thromboxane A2 (CTxA2), phenylephrine (PE), and 5-hydroxytryptamine (5-HT). On the basis of their ED50 values (dose of agonist, in mass units, that produced 50% of maximal response to that agonist), the order of vasoconstrictor potency was ANG II > or = AVP > ET-1 > CPA > 5-HT > or = PE > CTxA2. Dose-response curves to CPA were shallower and maximal responses were weaker than those produced by the other agonists. Maximal responses, the log ED50, and the slope of the dose-response curve to CPA were markedly potentiated in the presence of the nitric oxide (NO) synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME). Selective antagonism of A1 receptors increased renal blood flow and markedly attenuated CPA-induced renal vasoconstriction in the absence or presence of L-NAME but had no effect on the maximal responses to ANG II. Conversely, AT1 receptor antagonism attenuated renal vasoconstriction produced by ANG II but had little effect on the produced by CPA. These results suggest that endogenous NO modulates renal vasoconstriction produced by A1 receptor stimulation and provide evidence against an interaction between renovascular adenosine A1 and angiotensin AT1 receptors.
Barrett
R J
RJ
Department of Pharmacology, Whitby Research, Richmond, Virginia 23261.
Droppleman
D A
DA
D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001127:Arginine Vasopressin / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology; D007668:Kidney / Q000098:blood supply*; D019808:Losartan; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000502:physiology*; D010656:Phenylephrine / Q000494:pharmacology; D058914:Purinergic Antagonists; D051381:Rats; D017207:Rats, Sprague-Dawley; D018047:Receptors, Purinergic P1 / Q000187:drug effects / Q000502:physiology*; D012039:Regional Blood Flow / Q000187:drug effects; D012079:Renal Circulation / Q000187:drug effects / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology; D013777:Tetrazoles / Q000494:pharmacology; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*
D001713:Biphenyl Compounds; D007093:Imidazoles; D058914:Purinergic Antagonists; D018047:Receptors, Purinergic P1; D013777:Tetrazoles; C024587:thromboxane A2, carbocyclic; C080758:N(6)-cyclopentyl-9-methyladenine; D000804:Angiotensin II; D001127:Arginine Vasopressin; D010656:Phenylephrine; D009569:Nitric Oxide; D012701:Serotonin; C048599:N(6)-cyclopentyladenosine; D013928:Thromboxane A2; D001120:Arginine; D000225:Adenine; D019808:Losartan; D000241:Adenosine; D019331:NG-Nitroarginine Methyl Ester