Augmented agonist-induced Ca(2+)-sensitization of coronary artery contraction in genetically hypertensive rats. Evidence for altered signal transduction in the coronary smooth muscle cells.
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.
Satoh
S
S
II. Physiologisches Institut, Universität Heidelberg, Germany.
Kreutz
R
R
Wilm
C
C
Ganten
D
D
Pfitzer
G
G
D008841:Actin Cytoskeleton / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000819:agonists / Q000378:metabolism / Q000494:pharmacology*; D002463:Cell Membrane Permeability / Q000187:drug effects; D005576:Colforsin / Q000494:pharmacology; D003331:Coronary Vessels / Q000187:drug effects* / Q000502:physiology; D004928:Escin / Q000494:pharmacology; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D006973:Hypertension / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012701:Serotonin / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology*
D005576:Colforsin; D012701:Serotonin; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D011189:Potassium Chloride; D004928:Escin; D002118:Calcium