Alpha 1-adrenergic stimulation of renal Na reabsorption requires glucose metabolism

Abstract

The effect of glucose on renal responses to alpha 1-adrenergic stimulation was examined in isolated rat kidneys perfused with 5 mM lactate, 5 mM alanine, 0.5 mM pyruvate, and 0.2 mM mercaptopicolinic acid. Adding 5 mM glucose to this perfusate vasodilated the kidneys and raised the glomerular filtration rate (GFR) and free water clearance without altering fractional sodium excretion. alpha 1-Adrenergic actions were evaluated with norepinephrine (NE, 60 nM), methoxamine (600 nM), and prazosin (1 microM). Glucose altered neither the vasoconstriction nor the reduction in GFR produced by NE and methoxamine but increased the antinatriuretic responses (P less than 0.001). Glucose was required for prazosin to inhibit the effect of NE on sodium and lithium excretion. The nonmetabolized glucose analogue, alpha-methyl-D-glucoside (5 mM), did not increase the antinatriuretic response to NE, therefore glucose metabolism and not Na cotransport stimulated the alpha 1-adrenergic response. Glucose did not alter alpha 1-adrenoceptor number or binding affinity for prazosin in renal cortical homogenates. We conclude that glucose metabolism in the proximal tubule is involved in the stimulation of sodium reabsorption by alpha 1-adrenoceptor agonists.