Unmasking sensitive alpha 2-adrenoceptor-mediated renal vasoconstriction in conscious rats.
Renal vascular reactivity to intrarenal arterial boluses of norepinephrine (NE), phenylephrine (PHE; alpha 1-agonist), and guanabenz (GBZ; alpha 2-agonist) was assessed in conscious, freely moving, chronically instrumented, normotensive Wistar rats. Dose-response curves (DRCs) were obtained in the absence and cumulative presence of propranolol (PROP; beta-antagonist), corynanthine (CORY; alpha 1-antagonist) and idazoxan (IDX; alpha 2-antagonist) to estimate effective dosages (ED) required for 15 and 75% peak reductions in renal blood flow. The PHE DRC had a short shallow ED15 region, but was primarily linear with a steep slope. The GBZ DRC had a shallow slope. The NE DRC had a prolonged shallow phase in the ED15 region and a steep slope in the ED75 region. PROP had no effect on the DRCs. CORY caused a parallel rightward shift of the PHE DRC and had no effect on the GBZ DRC. After CORY, the shallow ED15 portion of the NE DRC was even more pronounced with a slope now identical to that of the GBZ DRC, whereas the ED75 region of the NE DRC was shifted rightward like the PHE DRC. IDX preferentially antagonized the ED15 regions of the GBZ and NE DRCs. In a second group of rats, the alpha 2-adrenoceptor antagonist, rauwolscine, was administered following base-line DRCs to demonstrate rightward shifts of the NE and GBZ DRCs when PHE DRCs remained unaffected. Therefore, when boluses of NE are injected into the rat kidney, the vasoconstrictive responses are a result of the activation of both alpha 1- and alpha 2-adrenoceptors.(ABSTRACT TRUNCATED AT 250 WORDS)
Wolff
D W
DW
Department of Physiology and Pharmacology, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem 27103.
Colindres
R E
RE
Strandhoy
J W
JW
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D004146:Dioxanes / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006143:Guanabenz / Q000494:pharmacology*; D006146:Guanidines / Q000494:pharmacology*; D019329:Idazoxan; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology*; D010656:Phenylephrine / Q000494:pharmacology*; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*; D012079:Renal Circulation / Q000187:drug effects*; D014661:Vasoconstriction / Q000187:drug effects*; D015016:Yohimbine / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D004146:Dioxanes; D006146:Guanidines; D011942:Receptors, Adrenergic, alpha; D010656:Phenylephrine; D015016:Yohimbine; D011433:Propranolol; D006143:Guanabenz; D009638:Norepinephrine; D019329:Idazoxan