ARK KATP channels involved in the contraction-induced attenuation oh alpha2 adrenergic vasoconstriction in rat hindlimb?

G. D. Thomas, J. Hansen, R. Victor

Research output: Contribution to journalArticlepeer-review

Abstract

We previously have shown that α2-adrenergic vasoconstriction is greatly attenuated by metabolic events in contracting rat hindlimb (AJP 266:H920, 1994), hut the underlying mechanism is not known. ATP-dependent potassium (KATP) channels in skeletal and vascular smooth muscle also may he modulated by changes in metabolic activity (eg, hypoxia or ischemia). Because opening of these channels hyperpolarizes and relaxes smooth muscle, we asked if the attenuated α2 vasoconstriction in contracting hindlimb is mediated by activation of KATP channels. To test this, we measured arterial pressure and femoral artery blood flow (Doppler) responses to brief intra-arterial hindlimb infusion of the selective α2-adrenergic agonist UK14304 (0.4-1.5 μg/min) in chloralose-anesthetized rats during: a) cumulative administration of the KATP channel opener diazoxide (5,10, 15, 2(1. 25 mg/kg. iv); and b) intermittent, tetanic hindlimb contractions before and after administration of the KATP channel blocker, glibenclamide (20 mg/kg, iv). In resting hindlimb, diazoxide attenuated α2 vaso-constriction dose dependently: conductance decreased by 51±3% before diazoxide vs 13±4% after 25 mg/kg diazoxide (n=6). Similarly, contraction attenuated α2 vasoconstriction: conductance decreased by 57±3% at rest vs 8±1% during contraction (n=6). In these same 6 rats, glibenclamide partially restored α2 vasoconstriction during contraction: conductance decreased by 49±5% at rest vs 22±3% during contraction. These data suggest that activation of KATP channels can attenuate α2-adrenergic vasoconstriction in contracting rai hindlimh and may be an important mechanism whereby blood flow is optimally distributed within skeletal muscles to meet metabolic demand.

Original languageEnglish (US)
Pages (from-to)A571
JournalFASEB Journal
Volume10
Issue number3
StatePublished - Dec 1 1996

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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