Comparison of the contractile and calcium-increasing properties of platelet-activating factor and endothelin-1 in the rat mesenteric artery and vein.
In the present study, the properties of endothelin-1 (ET-1) and platelet-activating factor (PAF) in inducing contraction and increased intracellular-free calcium level in rat mesenteric arteries and veins were studied. Furthermore, measurements of cytosolic ([Ca](c)) and nuclear ([Ca](n)) Ca(2+) were performed by confocal microscopy. PAF, at a concentration of 1 microM, and the selective ET(B) agonists, IRL-1620 and sarafotoxin S6C (100 nM), induced a marked constriction and increase in [Ca](i) in the mesenteric vein but not in the artery. On the other hand, endothelin-1 (1 - 100 nM) induced a significant concentration-dependent nifedipine-insensitive increase in tension and [Ca](i) in both arteries and veins. Those responses to endothelin-1 were significantly reduced by the ET(A) receptor antagonist, BQ-123 (10(-6) M), on both types of vessels, whereas the selective ET(B) receptor antagonist, BQ-788, inhibited only the venous responses. The mixed ET(A)/ET(B) receptor antagonist, SB 209670, reduced the ET-1-induced venous responses to the same level of that found in presence of BQ-123 or BQ-788. However, concomitant applications of BQ-123 and BQ-788 reduced the vasoconstriction below to that induced by ET(A) or ET(B) blockade without further affecting [Ca](i). PAF and the selective ET(B) agonists IRL-1620, induced a sustained increase of [Ca](c) and [Ca](n) solely in venous cells and ET-1 in both arterial and venous smooth muscle cells. Thus, PAF increases total intracellular calcium concentration and tension on the smooth muscle cells from venous origin only. Furthermore, ET-1-induced vasoactive as well as [Ca](i) and [Ca](n) increasing effects are mediated by distinct receptors on venous and arterial smooth muscles.
Claing
Audrey
A
CIHR Group in Immuno-Cardiovascular Interaction, Department of Pharmacology, Faculty of Medicine, Université de Sherbrooke, Sherbrooke (Québec) J1H 5N4, Canada.
Shbaklo
Hadia
H
Plante
Mirco
M
Bkaily
Ghassan
G
D'Orléans-Juste
Pedro
P
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000494:pharmacology / Q000502:physiology*; D008297:Male; D008638:Mesenteric Arteries / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D008642:Mesenteric Veins / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D010972:Platelet Activating Factor / Q000494:pharmacology / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000819:agonists / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*
D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D010972:Platelet Activating Factor; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin; D002118:Calcium