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Augmented agonist induced Ca2+-sensitization of coronary artery contraction in genetically hypertensive rats - evidence for altered signal transduction in the coronary smooth muscle cells

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Item Type:Article
Title:Augmented agonist induced Ca2+-sensitization of coronary artery contraction in genetically hypertensive rats - evidence for altered signal transduction in the coronary smooth muscle cells
Creators Name:Satoh, S. and Kreutz, R. and Wilm, C. and Ganten, D. and Pfitzer, G.
Abstract:The Ca2+ responsiveness of vascular smooth muscle myofilaments is not unique: it is increased during neuro-humoral activation and decreased during beta-adrenergic stimulation. In this study we tested whether an augmented Ca2+ responsiveness of smooth muscle myofilaments may contribute to the increased coronary tone observed in hypertension using beta-escin-permeabilized coronary arteries from 3-mo-old stroke-prone spontaneously hypertensive rats (SHRSP) and their age matched normotensive reference strain (WKY rats). In intact coronary arteries, the response to 5-hydroxytryptamine (5-HT) but not to KCl was larger in SHRSP than in WKY rats. In beta-escin permeabilized coronary arteries in which the receptor effector coupling is still intact, 5-HT enhanced force at constant submaximal (Ca2+) (pCa 6.38) to a greater extent in SHRSP. The Ca2+ sensitizing effect of 5-HT was mimicked by GTP gamma S (0.01-10 microM); again this effect was larger in SHRSP. In the absence of 5-HT or GTP gamma S the Ca2+ force relation was similar in both groups. Forskolin induced relaxation at constant submaximal (Ca2+). This desensitizing effect was smaller in SHRSP than in WKY rats. In conclusion, this study shows that intracellular signalling pathways involved in modulating the Ca2+ responsiveness of coronary smooth muscle myofilaments are altered in the genetically hypertensive animals favoring a hypercontractile state in the coronary circulation.
Keywords:Actin Cytoskeleton, Calcium, Cell Membrane Permeability, Coronary Vessels, Escin, Forskolin, Guanosine 5'-O-(3-Thiotriphosphate), Hypertension, Muscle Contraction, Potassium Chloride, Serotonin, Signal Transduction, Vascular Smooth Muscle, Animals, Rats
Source:Journal of Clinical Investigation
ISSN:0021-9738
Publisher:American Society for Clinical Investigation (U.S.A.)
Volume:94
Number:4
Page Range:1397-1403
Date:October 1994
Official Publication:https://doi.org/10.1172/JCI117475
PubMed:View item in PubMed

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