Document Detail

Changes in functional expression of alpha-1 adrenoceptors in hindlimb vascular bed of spontaneously hypertensive rats and their effects on oxygen consumption.
MedLine Citation:
PMID:  9694909     Owner:  NLM     Status:  MEDLINE    
Norepinephrine (NE) induces a sigmoidal dose-response curve for perfusion pressure and a bell-shaped curve for oxygen consumption (VO2) in the constant-flow perfused hindlimb of Wistar rats. These effects are now described in spontaneously hypertensive rats (SHR) and age-matched Wistar-Kyoto rats (WKY). In SHR, the pressure curve was shifted left- and upward whereas the VO2 curve was shifted left- but downward, when compared with WKY. In the presence of 10 microM propranolol, prazosin (2.5 nM) shifted the pressure and VO2 curves much more than yohimbine (0.1 microM) to the right in both strains and its effects were greater in SHR, suggesting that these effects were mediated largely by alpha-1 receptors, particularly in SHR. In the presence of propranolol plus yohimbine, the pressure curve was markedly shifted to the right by both the selective alpha-1A-antagonist 5-methylurapidil (3.3 nM), and by the alpha-1D antagonist BMY 7378 (0.1 microM) or SK&F 105854 (2 microM) in SHR but not in WKY. With respect to the VO2 curve, 5-methylurapidil attenuated the descending limb without affecting the ascending limb. Similar effects were also obtained with another alpha-1A antagonist 1 nM KMD-3213 in both SHR and WKY. In contrast, BMY and SK&F markedly inhibited the ascending limb of the VO2 curve. These results indicate that both alpha-1A- and alpha-1D subtypes are functionally up-regulated in SHR muscle vascular bed where the ascending limb of VO2 is predominantly mediated by the alpha-1D at a much lower concentration for NE than the descending limb which is predominantly mediated by the alpha-1A subtype.
J M Ye; E Q Colquhoun
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of pharmacology and experimental therapeutics     Volume:  286     ISSN:  0022-3565     ISO Abbreviation:  J. Pharmacol. Exp. Ther.     Publication Date:  1998 Aug 
Date Detail:
Created Date:  1998-09-02     Completed Date:  1998-09-02     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0376362     Medline TA:  J Pharmacol Exp Ther     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  599-606     Citation Subset:  IM    
Division of Biochemistry, School of Medicine, University of Tasmania, Hobart, Tasmania, Australia 7001.
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MeSH Terms
Adrenergic alpha-Agonists / pharmacology
Adrenergic alpha-Antagonists / pharmacology
Blood Pressure / drug effects,  physiology
Dose-Response Relationship, Drug
Hindlimb / blood supply
Hypertension / genetics*,  metabolism*
Muscle, Smooth, Vascular / metabolism*
Norepinephrine / pharmacology
Oxygen Consumption / genetics*,  physiology*
Rats, Inbred SHR
Rats, Inbred WKY
Receptors, Adrenergic, alpha-1 / agonists,  antagonists & inhibitors,  biosynthesis*
Regional Blood Flow / physiology
Vasoconstriction / drug effects
Reg. No./Substance:
0/Adrenergic alpha-Agonists; 0/Adrenergic alpha-Antagonists; 0/Receptors, Adrenergic, alpha-1; 51-41-2/Norepinephrine

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