Renal alpha 2-adrenergic receptors multiply and mediate sodium retention after prazosin treatment.

Renal nerve stimulation-induced antinatriuresis normally is mediated through post-synaptic alpha 1-adrenergic receptors; however, prazosin-induced alpha 1-adrenergic receptor blockade is associated clinically with sodium retention and not natriuresis. To study whether alpha 2-adrenergic receptors mediate renal nerve stimulation-induced antinatriuresis after chronic prazosin treatment, Sprague-Dawley rats were pretreated for 3 days with prazosin (3 mg/kg/day i.p. plus 0.15 mg/ml drinking water) or vehicle (untreated). In isolated perfused (Krebs-Henseleit; Ficoll, 3.5 g/dl, + albumin, 1.0 g/dl at 36 degrees C) kidneys from untreated rats, subpressor levels of renal nerve stimulation (approximately 1 Hz, 10 V, 1 msec) decreased (p less than 0.05) sodium (from 4.50 +/- 0.42 to 1.71 +/- .23 muEq/min) and urinary excretion rate (from 87.2 +/- 4.1 to 57.9 +/- 3.9 microliter/min). Adding prazosin (30 nM) to the perfusate completely (approximately 90%) reversed this effect (p less than 0.05), while alpha 2-adrenergic receptor blockade with yohimbine (300 nM) had no effect. In perfused kidneys from prazosin-treated rats, renal nerve stimulation decreased (p less than 0.05) sodium (from 3.24 +/- .40 to 1.32 +/- .27 muEq/min) and urinary excretion rate (from 78.7 +/- 5.0 to 54.1 +/- 5.3 microliter/min). However, adding prazosin (100 nM) to the perfusate produced only a slight, insignificant reversal of these effects; prazosin plus yohimbine were required to completely reverse the effects. These results suggest that renal nerve stimulation-induced sodium reabsorption was activated by alpha 1-adrenergic receptors in untreated rats and in part by alpha 2-adrenergic receptors in rats pretreated for 3 days with prazosin.(ABSTRACT TRUNCATED AT 250 WORDS)