Document Detail

Membrane potential-dependent and -independent vasodilation in small pulmonary arteries from chronically hypoxic rats.
MedLine Citation:
PMID:  9618397     Owner:  NLM     Status:  MEDLINE    
Chronic hypoxia is associated with altered pulmonary vasoreactivity, and it has been suggested that an increased response to voltage-dependent vasodilators may relate to enhanced Ca++ entry via voltage-dependent channels, secondary to depolarization. Few studies have been performed on small pulmonary arteries, and it is unknown whether they are depolarized after chronic hypoxia. We examined the resting membrane potential, and the actions of voltage-dependent (verapamil, levcromakalim) and -independent (isoproterenol, forskolin, papaverine) vasodilators in small ( approximately 300 microm internal diameter) pulmonary arteries from chronically hypoxic rats. The resting membrane potential was more positive in arteries after chronic hypoxia (control: -60 +/- 0.5 mV; hypoxic: -54.4 +/- 1.1 mV; P < .01), and this was reflected by a shift to the left of the response curves for K+ and 4-aminopyridine. In arteries constricted with prostaglandin F2alpha the response to verapamil and levcromakalim was increased after chronic hypoxia, although maximum prostaglandin F2alpha-induced tension was unchanged, which implies a reduction in voltage-independent constrictor mechanisms. Although vasorelaxation to isoproterenol was depressed in arteries from hypoxic rats, forskolin-induced relaxation was enhanced substantially, and because the response to the phosphodiesterase inhibitor papaverine was unchanged, we suggest that this reflects an up-regulation of adenylate cyclase. In conclusion, chronic hypoxia resulted in a significant depolarization in small pulmonary arteries, but this may explain only partly the increased efficacy of voltage-dependent vasodilators. Whether the reduction in voltage-independent constrictor mechanisms is related to the apparent up-regulation of adenylate cyclase remains to be elucidated.
R M Priest; T P Robertson; R M Leach; J P Ward
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of pharmacology and experimental therapeutics     Volume:  285     ISSN:  0022-3565     ISO Abbreviation:  J. Pharmacol. Exp. Ther.     Publication Date:  1998 Jun 
Date Detail:
Created Date:  1998-07-02     Completed Date:  1998-07-02     Revised Date:  2010-08-25    
Medline Journal Info:
Nlm Unique ID:  0376362     Medline TA:  J Pharmacol Exp Ther     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  975-82     Citation Subset:  IM    
Department of Allergy and Respiratory Medicine, UMDS Smooth Muscle Group, UMDS, St Thomas' Campus, London SE1 7EH, United Kingdom.
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MeSH Terms
Anoxia / physiopathology*
Body Weight / drug effects
Cromakalim / pharmacology
Dinoprost / metabolism*
Dose-Response Relationship, Drug
Heart Ventricles / drug effects
Isoproterenol / pharmacology
Membrane Potentials / drug effects,  physiology
Papaverine / pharmacology
Potassium Channel Blockers
Pulmonary Artery / drug effects*,  physiology
Rats, Wistar
Vasodilation / drug effects*
Vasodilator Agents / pharmacology*
Verapamil / pharmacology
Grant Support
//Wellcome Trust
Reg. No./Substance:
0/Potassium Channel Blockers; 0/Vasodilator Agents; 52-53-9/Verapamil; 551-11-1/Dinoprost; 58-74-2/Papaverine; 7683-59-2/Isoproterenol; 94470-67-4/Cromakalim

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