| Altered vascular reactivity and KATP channel currents in vascular smooth muscle cells from deoxycorticosterone acetate (DOCA)-salt hypertensive rats. | |
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MedLine Citation:
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PMID: 15505488 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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This study was designed to evaluate the contribution of ATP-dependent potassium (KATP) channels to the changes in vascular reactivity and spontaneous tone observed in vessels isolated from deoxycorticosterone acetate (DOCA)-salt hypertensive rats. In phenylephrine preconstricted aortic rings, cromakalim induced concentration-dependent, glibenclamide-sensitive relaxation. The concentration response curve to cromakalim was shifted to the right in DOCA-salt hypertensive rats (EC50: 0.850 +/- 0.100 microM) compared with SHAM-normotensive rats (0.108 +/- 0.005 microM), and the maximum relaxation (Emax) evoked by cromakalim was significantly lower in aortic rings from the DOCA group (68 +/- 2%) compared with the SHAM group (108 +/- 5%). The results were similar in endothelium-denuded rings. Spontaneous tone was observed in aortic rings (5 g preload) from DOCA-salt but not SHAM rats. Cromakalim abolished spontaneous tone and the effect was blocked by glibencamide. In whole cell patch clamp studies, increasing extracellular K concentrations from 5.4 to 140 mM and the administration of cromakalim evoked dramatic increases in KATP channel currents in aortic cells isolated from SHAM rats. In contrast, in aortic cells from DOCA-salt hypertensive rats, KATP channel currents were either absent or weak in response to challenges by elevated extracellular K and by cromakalim. These findings suggest that the function of KATP channels is impaired in smooth muscle cells from aorta of DOCA-salt hypertensive rats, which may contribute to the impaired vasodilatation and spontaneous tone observed in these rats. |
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Authors:
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Mahua Ghosh; Salma T Hanna; Rui Wang; J Robert McNeill |
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Publication Detail:
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Type: Comparative Study; Evaluation Studies; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of cardiovascular pharmacology Volume: 44 ISSN: 0160-2446 ISO Abbreviation: J. Cardiovasc. Pharmacol. Publication Date: 2004 Nov |
Date Detail:
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Created Date: 2004-10-26 Completed Date: 2005-05-16 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 7902492 Medline TA: J Cardiovasc Pharmacol Country: United States |
Other Details:
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Languages: eng Pagination: 525-31 Citation Subset: IM |
Affiliation:
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Department of Pharmacology, University of Saskatchewan, Saskatoon, Canada. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adenosine Triphosphate
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pharmacology,
physiology* Animals Aorta, Thoracic / drug effects, injuries, pathology Blood Pressure / drug effects Canada Cromakalim / antagonists & inhibitors, pharmacology Desoxycorticosterone Disease Models, Animal Dose-Response Relationship, Drug Drug Implants / administration & dosage Electrophysiology / methods Endothelium, Vascular / drug effects, injuries, pathology Glyburide / pharmacology Hypertension / chemically induced, drug therapy, pathology* Male Membrane Potentials / drug effects, physiology Muscle, Smooth, Vascular / drug effects, pathology*, physiopathology* Nephrectomy / methods Phenylephrine / antagonists & inhibitors, pharmacology Potassium Channels / classification, drug effects, physiology* Potassium Chloride / metabolism, pharmacology Rats Rats, Sprague-Dawley Vasoconstriction / drug effects, physiology Vasodilation / drug effects, physiology |
| Chemical | |
Reg. No./Substance:
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0/Drug Implants; 0/Potassium Channels; 10238-21-8/Glyburide; 56-65-5/Adenosine Triphosphate; 59-42-7/Phenylephrine; 64-85-7/Desoxycorticosterone; 7447-40-7/Potassium Chloride; 94470-67-4/Cromakalim |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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