Comparison of peptide and nonpeptide receptor-mediated responses in rat tail artery.
Chronic uremia and metabolic acidosis impair vascular responses to norepinephrine (NE) and also cause multiple metabolic defects in skeletal muscle. These studies were conducted to determine whether decreased vascular responsiveness resulted from putative second messenger metabolism. Tail arteries were used from rats with metabolic acidosis or nonacidotic uremia and from normal controls. In normal arteries, the maximal responses were the same for arginine vasopressin (AVP), NE, and mixtures of the two agonists, suggesting that the two receptor types use the same transduction mechanism. Nonetheless, qualitative differences exist between AVP- and NE-induced responses: (a) Concentration-response curves are steeper for AVP than for NE, (b) EC50 values are similar for AVP between inositol phosphates (IP assays) and contraction, but not for NE, and (c) arteries from rats with metabolic acidosis or uremia show selective blunting of biochemical and contractile responses to NE but not to AVP. We conclude that these metabolic derangements selectively affect alpha-adrenergic receptors, but not AVP receptors or the transduction mechanism leading to contraction.
Fox
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AW
Department of Medicine, Harvard Medical School, Brigham and Women's Hospital.
May
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RE
Mitch
W E
WE
D000138:Acidosis / Q000378:metabolism / Q000503:physiopathology; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology*; D001158:Arteries / Q000187:drug effects / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000032:analysis / Q000378:metabolism; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects*; D013623:Tail / Q000098:blood supply; D014511:Uremia / Q000378:metabolism / Q000503:physiopathology
D007295:Inositol Phosphates; D011942:Receptors, Adrenergic, alpha; D001127:Arginine Vasopressin; D009638:Norepinephrine