Journal article
Effects of Thiol Chelation on α1-Adrenoceptor-Induced Vasoconstriction In Vivo
Journal of cardiovascular pharmacology, Vol.46(5), pp.627-636
11/2005
DOI: 10.1097/01.fjc.0000181718.25323.91
Abstract
The aims of this study were to determine whether systemic injections of the lipophobic thiol chelator, para-hydroxymercurobenzoic acid (PHMBA) would reduce the vasoconstrictor responses elicited by the α1-adrenoceptor agonist, phenylephrine, in urethane-anesthetized rats by chelation of thiol residues in α1-adrenoceptors in vascular smooth muscle rather than voltage-sensitive Ca-channels (CaVERSUS-channels). The magnitudes and durations of the vasoconstrictor responses elicited by phenylephrine were markedly reduced after the injections of PHMBA. In contrast, the maximal phenylephrine-induced responses were not affected whereas the durations of these responses were markedly attenuated after injection of the CaVERSUS-channel blocker, nifedipine. Nifedipine elicited pronounced and sustained falls in mean arterial blood pressure and vascular resistances in PHMBA-treated rats. Moreover, the vasodilator actions of the nitric oxide-donor, sodium nitroprusside were minimally attenuated by PHMBA whereas they were markedly attenuated by nifedipine. These findings support evidence that the vasoconstrictor responses due to activation of α1-adrenoceptors are initiated by mobilization of intracellular pools of Ca whereas they are sustained by opening of CaVERSUS-channels. These findings also suggest that PHMBA diminishes the vasoconstrictor effects of phenylephrine by chelation of thiol residues in α1-adrenoceptors rather than by blockade of CaVERSUS-channels, and that chelation of these thiol residues prevents agonist occupation and/or activation of these receptors and subsequent mobilization of intracellular pools of Ca.
Details
- Title: Subtitle
- Effects of Thiol Chelation on α1-Adrenoceptor-Induced Vasoconstriction In Vivo
- Creators
- Azizul HoqueJoy Owen - University of GeorgiaJames Bates - University of Iowa, AnesthesiaStephen Lewis - Case Western Reserve University
- Resource Type
- Journal article
- Publication Details
- Journal of cardiovascular pharmacology, Vol.46(5), pp.627-636
- Publisher
- Lippincott Williams & Wilkins, Inc
- DOI
- 10.1097/01.fjc.0000181718.25323.91
- ISSN
- 0160-2446
- eISSN
- 1533-4023
- Language
- English
- Date published
- 11/2005
- Academic Unit
- Anesthesia
- Record Identifier
- 9984424843402771
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