Localization of alpha 2-adrenoceptor-mediated increase in renal Na+, K+, and water excretion.
Free-flow micropuncture and clearance studies were conducted in male Sprague-Dawley rats to investigate the effects of alpha 2-adrenoceptor stimulation on Na+, K+, and water transport along the nephron. Intravenous infusion of the selective alpha 2-adrenoceptor agonist B-HT 933 at 1 mg X kg-1 X h-1 increased urinary flow rate from 16.2 +/- 3.6 to 84.8 +/- 11.9 microliter/min, fractional excretion of Na+ from 1.36 +/- 0.31 to 3.57 +/- 0.52%, and fractional excretion of K+ from 26.9 +/- 3.0 to 42.3 +/- 2.2%, The diuresis, saluresis, and kaliuresis were not the result of increases in glomerular filtration rate or mean arterial blood pressure. Urine osmolality decreased from 1,126 +/- 177 to 325 +/- 33 mosmol/kg water and in 8 of the 11 animals studied B-HT 933 decreased urine osmolality to hyposmotic levels, suggesting a possible interaction between the alpha 2-adrenoceptor agonist and vasopressin. The alpha 2-adrenoceptor antagonist yohimbine (0.25/mg bolus, iv) inhibited the diuresis, saliuresis, and kaliuresis. In micropuncture studies, B-HT 933 was without effect on single-nephron glomerular filtration rate or on Na+, K+, and water transport along the superficial proximal tubule, loop of Henle, or distal tubule. Thus stimulation of alpha 2-adrenoceptors increases Na+, K+, and water excretion by inhibiting tubule reabsorption of these substances at nephron sites beyond the superficial distal tubule, most likely by the collecting tubule.
D000818:Animals; D001381:Azepines / Q000494:pharmacology; D004231:Diuresis / Q000187:drug effects; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009318:Natriuresis / Q000187:drug effects; D011188:Potassium / Q000652:urine*; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D015016:Yohimbine / Q000494:pharmacology
D001381:Azepines; D011942:Receptors, Adrenergic, alpha; D015016:Yohimbine; C015603:azepexole; D011188:Potassium