Alpha 2-adrenoceptor antagonism of vasopressin-induced changes in sodium excretion.
Alpha 2-adrenoceptor agonists attenuate vasopressin-mediated changes in water excretion. The effects on sodium excretion, however, are unclear. We therefore utilized the nonrecirculating isolated perfused rat kidney to study the direct effects of vasopressin and alpha 2-adrenoceptor stimulation on sodium and water excretion in the absence of systemic regulatory systems. The perfusate was a Krebs-Henseleit solution (3.5 g/100 ml Ficoll; 1.0% albumin; 36 degrees C) containing prazosin (30 nM) and propranolol (100 nM) to prevent effects of alpha 1- and beta-adrenoceptor stimulation. Vasopressin (10 microU/ml) produced a significant (P less than 0.05) decrease in both water and sodium excretion. Potassium excretion was not significantly altered. Alpha 2-Adrenoceptor stimulation with l-epinephrine (28 nM) reversed (P less than 0.05) the effects of vasopressin on water and sodium excretion. To confirm that this attenuation was mediated by alpha 2-adrenoceptors, an alpha 2-adrenoceptor antagonist, yohimbine, was administered. Yohimbine (300 nM) blocked the effects of epinephrine on sodium and water excretion (P less than 0.05). The adenosine P-site agonist, SQ 22,536 (100 microM), which mediates its effects through inhibition of adenylate cyclase, produced the same reversal as that of epinephrine on vasopressin-mediated changes. Thus alpha 2-adrenoceptor stimulation antagonized the effects of vasopressin on both water and sodium excretion at the renal level. A corollary to this conclusion is that the function-specific activation of renal adenylate cyclase determines the effect of alpha 2-adrenoceptor stimulation.
Smyth
D D
DD
Umemura
S
S
Pettinger
W A
WA
D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001834:Body Water / Q000378:metabolism; D004837:Epinephrine / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009318:Natriuresis / Q000187:drug effects; D010477:Perfusion; D011188:Potassium / Q000652:urine; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D014556:Urine; D014667:Vasopressins / Q000494:pharmacology*; D015016:Yohimbine / Q000494:pharmacology
D011942:Receptors, Adrenergic, alpha; D014667:Vasopressins; C017759:9-(tetrahydro-2-furyl)-adenine; D015016:Yohimbine; D000225:Adenine; D011188:Potassium; D004837:Epinephrine