Specific alpha 1-, alpha 2-, and beta-responses to norepinephrine in pyruvate-perfused rat kidneys

We compared the effects of alpha- and beta-adrenergic agonists on vascular resistance, gluconeogenesis (GNG), and electrolyte excretion in pyruvate-perfused rat kidneys. Norepinephrine (NE) (15-60 nM) increased vascular resistance (2-19%) and GNG (42-49%) and decreased fractional excretion of Na (18-34%), Cl (38-48%), and K (13-27%). Prazosin and yohimbine blocked the vasoconstrictor but not the antinatriuretic response. Prazosin revealed an antiphosphaturic and inhibited the gluconeogenic response. Propranolol blocked the effect on Na and Cl (66%) and K excretion (100%). Methoxamine (0.6-1 microM) maximally increased GNG (40-52%) with little effect on vascular resistance (+0-9%) and NaCl excretion (-0-11%). Adding glucose to the perfusate increased methoxamine's effects on electrolyte excretion and vascular resistance. Mercaptopicolinate did not alter methoxamine's effects during pyruvate perfusion. Clonidine (0.1 microM) decreased phosphate excretion without vasoconstriction or antinatriuresis; 0.5-1 microM vasoconstricted and decreased NaCl excretion. Isoproterenol (0.1 microM) vasodilated and decreased Na (25%), Cl (40%), and K excretion (20%). Thus alpha 1- and beta-receptors could account for the effect of NE on GNG and K reabsorption, respectively. Synergism of alpha 1, alpha 2, and beta were required for full antinatriuresis. Glucose increased alpha 1-stimulated vasoconstriction and antinatriuresis. Blocking alpha 1-receptors revealed an alpha 2-like antiphosphaturic response.