Intrahepatic adenosine-mediated activation of hepatorenal reflex is via A1 receptors in rats.
Previous studies have shown that intrahepatic adenosine is involved in activation of the hepatorenal reflex that regulates renal sodium and water excretion. The present study aims to determine which subtype of adenosine receptors is implicated in the process. Mean arterial pressure, portal venous pressure and flow, and renal arterial flow were monitored in pentobarbital anesthetized rats. Urine was collected from the bladder. Intraportal administration of 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), a selective adenosine A1 receptor antagonist, increased urine flow by 24%, 89%, and 143% at the dose of 0.01, 0.03, and 0.1 mg x kg(-1), respectively; in contrast, DPCPX, when administered intravenously at the same doses, only increased urine flow by 0%, 18%, and 36%. The increases in urine flow induced by intraportal administration of DPCPX were abolished in rats with liver denervation. Intrahepatic infusion of adenosine significantly decreased urine flow and this response was abolished by intraportal administration of DPCPX. Neither intraportal nor intravenous administration of 3,7-dimethyl-1-propargylxanthine, a selective adenosine A2 receptor antagonist, showed significant influence on urine flow. Systemic arterial pressure, renal blood flow and glomerular filtration rate were unaltered by the administration of any of the drugs. In conclusion, intrahepatic adenosine A1 receptors are responsible for the adenosine-mediated hepatorenal reflex that regulates renal water and sodium excretion.
Ming
Zhi
Z
Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Manitoba, 753 McDermot Avenue, Winnipeg, MB R3E 0T6, Canada.
Lautt
W Wayne
WW
D000241:Adenosine / Q000378:metabolism* / Q000494:pharmacology; D058916:Adenosine A1 Receptor Antagonists; D000818:Animals; D001783:Blood Flow Velocity; D001794:Blood Pressure; D003714:Denervation; D004305:Dose-Response Relationship, Drug; D007275:Injections, Intravenous / Q000379:methods; D007668:Kidney / Q000187:drug effects / Q000294:innervation / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000294:innervation / Q000378:metabolism*; D008297:Male; D009318:Natriuresis / Q000187:drug effects; D017082:Portal Pressure; D011169:Portal Vein / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043682:Receptor, Adenosine A1 / Q000378:metabolism*; D043683:Receptors, Adenosine A2 / Q000378:metabolism; D012018:Reflex / Q000187:drug effects; D012077:Renal Artery / Q000502:physiology; D013805:Theobromine / Q000008:administration & dosage / Q000031:analogs & derivatives; D014554:Urination / Q000187:drug effects; D014970:Xanthines / Q000008:administration & dosage
D058916:Adenosine A1 Receptor Antagonists; D043682:Receptor, Adenosine A1; D043683:Receptors, Adenosine A2; D014970:Xanthines; C057837:3,7-dimethyl-1-propargylxanthine; C051360:1,3-dipropyl-8-cyclopentylxanthine; D000241:Adenosine; D013805:Theobromine