Prazosin-Induced Alterations in Renal a-Adrenergic Receptor Function

Chronic (3-day) treatment with prazosin causes an increase in renal a2-adrenergic receptor density and the relocation of renal tubular a2-adrenergic receptors from extrajunctional to postjunctional sites. We investigated whether chronic prazosin treatment (2 mg/kg, i.p.) caused a functional alteration of other renal a2-adrenergic receptors, using the isolated perfused rat kidney. Prazosin significantly reduced blood pressure and increased heart rate during the 3-day treatment. Renal nerve stimulation (2-8 Hz, 10 V, 1 msec) caused a frequency-dependent increase in renovascular resistance, which was potently blocked by prazosin in vitro in both control and prazosin-treated rat kidneys. The vasoconstrictor response to the a2-adrenergic receptor-selective agonist BHT 933 (3-300 fjM) was significantly higher in kidneys from prazosin-treated rats. Yohimbine (3-300 nM) potentiated the response to renal nerve stimulation in both treatment groups. The increase in vascular resistance following renal nerve stimulation was lower in kidneys from prazosin-treated rats, but the response to the at-adrenergic receptor agonist methoxamine (0.3-1 /nM) was unchanged. Further studies revealed that renal nerve stimulation-evoked norepinephrine release from prazosin-treated rat kidneys was significantly lower than release from untreated controls. This response could be normalized to control levels by a combination of cocaine (10 /LIM) and yohimbine (100 nM). Thus, chronic prazosin treatment caused enhanced a2-adrenergic receptor-mediated vasoconstriction and facilitated renal prejunctional inhibitory mechanisms. We conclude that with chronic a,-adrenergic receptor blockade there is increased a2-adrenergic receptor function in at least two and possibly three sites in the kidney; these include postjunctional tubular, prejunctional vascular, and possibly extrajunctional vascular sites. (Hypertension 9 [Suppl III]: III-125-III-129, 1987)