Identification of alpha 1-adrenoceptor subtypes involved in the antinatriuretic response to intrarenal infusion of phenylephrine

Eur J Pharmacol. 1995 Dec 4;287(1):1-6. doi: 10.1016/0014-2999(95)00469-9.

Abstract

It is reported that alpha 1-adrenoceptors located in the renal vasculature and renal tubules play a major role in mediating antinatriuretic response to renal nerve stimulation as well as to the infusion of alpha 1-adrenoceptor agonist. In the present study intrarenal infusion of alpha 1-adrenoceptor agonist phenylephrine (0.25 microgram/kg/min) to Inactin-anesthetized Sprague-Dawley rats produced approximately 50% reduction in urine output, Na+ excretion and glomerular filtration rate without causing significant alterations in mean blood pressure, heart rate and fractional Na+ excretion. These changes were completely abolished by prior intrarenal infusion of prazosin (0.5 microgram/kg/min for 30 min). In separate groups of experiments, the animals received either a selective irreversible alpha 1A-adrenoceptor antagonist, SZL-49 [1-(4-amino-6,7-dimethoxy-2-quinazolinyl)-4-(2-bicyclo[2,2,2]octa-2,5- diene-2-carbonyl)piperazine], or an alpha 1B-adrenoceptor antagonist, chloroethylclonidine, intrarenally prior to phenylephrine infusion. Neither SZL-49 nor chloroethylclonidine alone significantly altered glomerular filtration rate and renal electrolyte excretion. However, SZL-49 (0.15 microgram/kg/min), but not chloroethylclonidine (50 micrograms/kg/min), completely abolished phenylephrine-induced changes in urine output, Na+ excretion and glomerular filtration rate. These results demonstrate that phenylephrine decreases urine output and Na+ excretion, mainly due to a reduction in glomerular filtration rate resulting from activation of alpha 1A-adrenoceptors, and that proximal tubular alpha 1A- or alpha 1B-adrenoceptors do not appear to contribute to this response.

MeSH terms

  • Adrenergic alpha-Agonists / administration & dosage
  • Adrenergic alpha-Agonists / pharmacology*
  • Animals
  • Glomerular Filtration Rate / drug effects
  • Male
  • Natriuresis / drug effects*
  • Phenylephrine / administration & dosage
  • Phenylephrine / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Adrenergic, alpha-1 / drug effects*
  • Receptors, Adrenergic, alpha-1 / metabolism
  • Sodium / urine
  • Vasoconstriction

Substances

  • Adrenergic alpha-Agonists
  • Receptors, Adrenergic, alpha-1
  • Phenylephrine
  • Sodium