Axial stretch modifies contractility of porcine coronary arteries by a protein kinase C-dependent mechanism.
Large coronary arteries undergo marked circumferential and axial deformations due to changes in blood pressure and gross movements of the ventricular wall during systole and diastole. The present study was designed to investigate 1) whether axial stretch of large coronary arteries influences the sensitivity to vasoconstrictors, 2) the mechanisms mediating stretch-dependent changes in vascular sensitivity. Endothelium-denuded cylindrical segments from large porcine coronary arteries were studied under isometric conditions using a balloon-based impedance planimetric technique. In segments subjected to a pressure of 60 mmHg, 20% axial stretch caused a left-ward shift of the concentration-response curves for K+ and 5-hydroxytryptamine (5-HT). Enhancement of vascular sensitivity to 5-HT induced by axial stretch was observed also in maximally K+-depolarized coronary arteries. Protein kinase C inhibition by calphostin C (1 microM) slightly decreased the spontaneous resting tone at 60 mmHg and inhibited the leftward shift of the concentration-response curve for 5-HT elicited by axial stretch. These results suggest that axial stretch of the vessel wall enhances the sensitivity of coronary arteries to vasoconstrictors by a protein kinase C-dependent mechanism.
Tankó
L B
LB
Department of Pharmacology, University of Aarhus, Denmark. lbt@ccbr.dk
Simonsen
U
U
Matrougui
K
K
Gregersen
H
H
Frøbert
O
O
Bagger
J P
JP
Mikkelsen
E O
EO
D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D017097:Electric Impedance; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007091:Image Processing, Computer-Assisted; D007537:Isometric Contraction / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D009281:Naphthalenes / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012701:Serotonin / Q000494:pharmacology*; D013552:Swine; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D004791:Enzyme Inhibitors; D009281:Naphthalenes; D014662:Vasoconstrictor Agents; C061465:calphostin complex; D012701:Serotonin; D011493:Protein Kinase C; D011188:Potassium