Renovascular actions of adenosine in the isolated perfused rat kidney: possible underlying mechanisms.
We studied the renovascular action of adenosine on isolated perfused rat 10 min after drug injections. Adenosine was applied intraarterially as a single bolus injection in logarithmically increasing doses (0.3-30 microg). Adenosine treatment induced a biphasic vascular-response, namely, an initial vasoconstriction followed by a long-lasting vasodilation. Pretreatment with 0.1. 0.3, or 1.0 mM theophylline or quinidine (2 microg/ml) significantly depressed both components of the adenosine response. The vasoconstrictor response to adenosine was not affected by either 0.5 or 1.0 microg/ml dihydroergocristine. whereas the vasodilatory response was dose-dependently reduced. The biphasic response to adenosine was markedly depressed by 10 microg/ml indomethacin and was augmented by combining this agent with quinidine. We studied the possible roles of the platelet activating factor (PAF) and nitric oxide-cGMP systems in the renovascular actions of adenosine. Tebokan (a PAF antagonist) antagonized both components of the response, but methylene blue (MM) reduced only the pressory part Electron-microscopic examination of kidneys exposed for 15 min to MM showed some acute degenerative alterations and constriction in the glomeruli. From these findings, we conclude that the P1/A1, and P2x purinoceptors, the prostaglandins, PAF, and the NO-cGMP systems have a share in the renovascular actions of adenosine.
Küçükhüseyin
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C
Department of Pharmacology, Cerrahpaşa Medical Faculty, University of Istanbul, Turkey. tahic@istanbul.edu.tr
Akbaş
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Silan
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C
Barlas
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A
Yillar
D O
DO
Seçkin
I
I
D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D005260:Female; D006157:Guanosine Monophosphate / Q000502:physiology; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects / Q000648:ultrastructure; D008297:Male; D009569:Nitric Oxide / Q000502:physiology; D010972:Platelet Activating Factor / Q000494:pharmacology; D011453:Prostaglandins / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011983:Receptors, Purinergic / Q000187:drug effects; D012079:Renal Circulation / Q000187:drug effects*; D013564:Sympathetic Nervous System / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
D010972:Platelet Activating Factor; D011453:Prostaglandins; D011983:Receptors, Purinergic; D014665:Vasodilator Agents; D009569:Nitric Oxide; D006157:Guanosine Monophosphate; D000241:Adenosine