Prazosin-induced alterations in renal alpha-adrenergic receptor function.
Chronic (3-day) treatment with prazosin causes an increase in renal alpha 2-adrenergic receptor density and the relocation of renal tubular alpha 2-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 alpha 2-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 alpha 2-adrenergic receptor-selective agonist BHT 933 (3-300 microM) 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 alpha 1-adrenergic receptor agonist methoxamine (0.3-1 microM) 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 microM) and yohimbine (100 nM). Thus, chronic prazosin treatment caused enhanced alpha 2-adrenergic receptor-mediated vasoconstriction and facilitated renal prejunctional inhibitory mechanisms. We conclude that with chronic alpha 1 adrenergic receptor blockade there is increased alpha 2-adrenergic receptor function in at least two and possibly three sites in the kidney; these include postjunctional tubular, prejunctional vascular, and possibly extra-junctional vascular sites.
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D003042:Cocaine / Q000494:pharmacology; D004558:Electric Stimulation; D007022:Hypotension / Q000139:chemically induced; D066298:In Vitro Techniques; D007668:Kidney / Q000294:innervation / Q000648:ultrastructure*; D008297:Male; D011224:Prazosin / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects* / Q000502:physiology; D012079:Renal Circulation; D013610:Tachycardia / Q000139:chemically induced; D014655:Vascular Resistance; D014661:Vasoconstriction; D015016:Yohimbine / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D011942:Receptors, Adrenergic, alpha; D015016:Yohimbine; D003042:Cocaine; D011224:Prazosin