Subtype-selective alpha-1 adrenoceptor alkylation in the rat kidney and its effect on the vascular pressor response.
Separate genes for alpha-1A and alpha-1B adrenoceptors have now been identified. Whereas alpha-1 adrenoceptors are known to mediate rat renal vasoconstriction, the relative importance of these alpha-1 adrenoceptor subtypes was unknown. We cannulated the right suprarenal artery of anesthetized male Sprague-Dawley rats to permit administration of the alpha-1A and alpha-1B alkylating antagonists, SZL-49 (SZL) and chloroethylclonidine (CEC), respectively, directly into the right kidney. Treated kidneys were homogenized to identify the doses of SZL and CEC that caused the maximum reductions in Bmax for [3H]prazosin, the relatively nonselective alpha-1 adrenoceptor antagonist. In other rats, a Doppler flow probe was placed around the right renal artery, and dose-peak response curves for boluses of the alpha-1 adrenoceptor agonist phenylephrine (PHE) were generated before and after supramaximal dosages of SZL or CEC. Renal vasoconstriction to PHE was nearly obliterated by SZL. In contrast, CEC caused only a modest rightward shift in the PHE DRC. SZL also abolished the renal vascular response to two other alpha-1 adrenoceptor agonists, cirazoline and methoxamine. Our data support the conclusion that the alpha-1 adrenoceptors at the level of the rat renal resistance vessels are predominantly alpha-1A adrenoceptors.
Midwest Hypertension Research Center, Creighton University Medical Center, Omaha, Nebraska.
A M
AM
Elhawary
W A
WA
Pettinger
D W
DW
Wolff
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000478:Alkylation; D000818:Animals; D003000:Clonidine / Q000031:analogs & derivatives / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D007668:Kidney / Q000098:blood supply / Q000378:metabolism*; D008297:Male; D008729:Methoxamine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011224:Prazosin / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D012077:Renal Artery / Q000187:drug effects
D000317:Adrenergic alpha-Antagonists; D007093:Imidazoles; D011942:Receptors, Adrenergic, alpha; C051307:SZL 49; D010656:Phenylephrine; C051731:chlorethylclonidine; D008729:Methoxamine; D003000:Clonidine; C014282:cirazoline; D011224:Prazosin