Identification of alpha 1-adrenoceptor subtypes involved in the antinatriuretic response to intrarenal infusion of phenylephrine.
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.
Chen
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Institute for Cardiovascular Studies, University of Houston, TX 77204-5515, USA.
Lokhandwala
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MF
D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D005919:Glomerular Filtration Rate / Q000187:drug effects; D008297:Male; D009318:Natriuresis / Q000187:drug effects*; D010656:Phenylephrine / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects* / Q000378:metabolism; D012964:Sodium / Q000652:urine; D014661:Vasoconstriction
D000316:Adrenergic alpha-Agonists; D018340:Receptors, Adrenergic, alpha-1; D010656:Phenylephrine; D012964:Sodium