Alpha 2-adrenoceptors determine the response to nitric oxide inhibition in the rat glomerulus and proximal tubule.
Arginine-derived nitric oxide exerts control over the processes of glomerular filtration and tubular reabsorption. The tonic influence of nitric oxide over both of these is eliminated by renal denervation. The hypothesis that the renal nerves function, in this regard, via the activation of alpha 2-adrenoceptors was tested by renal micropuncture. The physical determinants of glomerular filtration and proximal tubular reabsorption were assessed in Munich-Wistar rats before and during the administration of the nitric oxide synthase inhibitor NG-monomethyl L-arginine (L-NMMA). In one set of studies, the systemic infusion of the alpha 2-agonist B-HT 933 rendered nephron GFR, nephron plasma flow, and proximal reabsorption sensitive to reduction by L-NMMA after renal denervation. In a second set of studies, the infusion of the alpha 2 receptor antagonist, yohimbine, to rats with renal nerves intact was found to suppress the effects of L-NMMA on nephron plasma flow and proximal reabsorption. The effects of L-NMMA on nephron GFR and nephron plasma flow, afferent and efferent arteriolar resistances, and proximal reabsorption correlated with the level of underlying alpha 2-adrenergic activity. The activation of renal alpha 2-adrenoceptors increases the influence of arginine-derived nitric oxide in the glomerulus and proximal tubule.
Thomson
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SC
San Diego Veterans Affairs Medical Center, La Jolla, CA, USA.
Vallon
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D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001381:Azepines / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006439:Hemodynamics; D007678:Kidney Glomerulus / Q000187:drug effects / Q000294:innervation* / Q000502:physiology; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000294:innervation* / Q000502:physiology; D008297:Male; D008954:Models, Biological; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D051381:Rats; D017208:Rats, Wistar; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects*
D000316:Adrenergic alpha-Agonists; D001381:Azepines; D004791:Enzyme Inhibitors; D018341:Receptors, Adrenergic, alpha-2; D009569:Nitric Oxide; D001120:Arginine; C015603:azepexole; D019331:NG-Nitroarginine Methyl Ester