Alpha adrenoceptor agonist stimulation of oxygen consumption in rat proximal and distal nephrons.
Selective alpha-1 and alpha-2 adrenergic agonists were used to test the hypothesis that both receptor subtypes increase transcellular Na+ transport in the nephron. Oxygen consumption (QO2) was used as an index of transcellular transport and provided a continuous dynamic record of the tubules' response to an agonist. Both alpha-1 and alpha-2 adrenoceptor agonists produced a linear dose-related increase in QO2 at a steeper slope than the control in proximal and distal nephron segments. Stimulation of QO2 by the adrenergic agonists did not occur in the presence of ouabain and did not exceed the maximal respiratory rate achieved with nystatin. The response was determined to be a receptor-mediated increase in the ouabain-sensitive component of respiration. An inactive stereoisomer of epinephrine produced no effect, and adrenergic antagonists inhibited the stimulation by the respective agonists. Adrenergic agonists stimulated QO2 in proximal segments to a much greater degree than observed with suspensions of distal segments. These results are consistent with the density of adrenoceptors on nephrons reported in radioligand binding and autoradiographic studies. The alpha-1 agonists, cirazoline and phenylephrine, had similar dose-response curves and stimulated proximal tubules more than distal tubules. The alpha-2 agonists, guanabenz, UK 14,304 and B-HT 933, equivalently stimulated QO2 in distal tubules, but a spectrum of enhanced oxygen consumption was observed in proximal nephrons. Although both alpha adrenoceptor subtypes increased QO2 in proximal and distal nephrons, the mechanisms are likely to be different.
Gesek
F A
FA
Department of Physiology and Pharmacology, Wake Forest University Medical Center, Winston-Salem, North Carolina.
Strandhoy
J W
JW
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D001381:Azepines / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006143:Guanabenz / Q000494:pharmacology; D008297:Male; D009399:Nephrons / Q000187:drug effects* / Q000378:metabolism; D009761:Nystatin / Q000494:pharmacology; D010042:Ouabain / Q000494:pharmacology; D010101:Oxygen Consumption / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000378:metabolism
D000316:Adrenergic alpha-Agonists; D001381:Azepines; D009761:Nystatin; D010042:Ouabain; D012964:Sodium; C015603:azepexole; D006143:Guanabenz