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Arteries, veins and endothelium-dependant relaxation: Cellular effects
4
THROMBOSIS RESEARCH
ZRTERIES, VEINS AND ENDOTHELIUM-DEPENDANT EFFECTS. M. FELETOU, FONDAX Groupe de Recherches Servier, FRANCE
Suppl.
VII,
RELAXATION
: CELLULAR
7 rue Amp&e
92800 Puteaux
1987
designed to determine the cellular mechanism underlying the Experiments were differences in endotheliumdependant responses to acetylcholine between arteries and veins. Using bioassay and electrophysiological techniques, the effect of endotheliumdependant relaxing factor (EDRF) released from the canine femoral artery of the dog was artery of the dog, the aorta of the compared in various vessels ; namely : the coronary rat, and the portal veins of both species. During bioassay experiments, the EDRF released under basal condition and during exposure to acetylcholine induced comparable relaxations of the canine coronary artery and rat aorta (aproximatively 35 %, for the basal release, and 75 %, for the stimulated release, of the contraction induced respectively by prostaglandin F2Q! and phenylephrine). spontaneous contractions were In contrast neither the canine nor the rat portal vein influenced by EDRF. Similarly EDRF was without effect on the portal veins contracted with phenylephrine. EDRF induced transient hyperpolarization of the canine coronary artery (average 11 mv). Neither the relaxation nor the hyperpolarization were sensitive to indomethacin excluding the intervention of prostanoids. However ouabain and potassium-free solution prevented the hyperpolarization but failed to abolish the relaxation of the canine coronary artery. Return to control solution (5.9 mMK+) after incubation in potassium free solution caused relaxation and hyperpolarization (average 17 mv) which demonstrates the existence of a sodium-potassium pump on this tissue. EDRF did not induce changes either in the membrane potential or the amplitude or the frequency of the spikes of the rat portal vein.
After contraction with prostglandin F2a ,sodium nitroprusside induced full relaxation of abolish the the canine coronary artery (ED50 = - 7.42 + 0.24) but failed to completely spontaneous activity of the rat portal vein (ED50 : - 5.03 + 0.3). So sodium nitroprusside was 250 times more effective on canine coronary artery than on rat portal vein. These experiments suggest that EDRF is not species specific as canine coronary artery and rat aorta behave identically. EDRF induces hyperpolarization of vascular smooth muscle of canine coronary artery probably by activating the Na+,K+ pump but this effect only partially explain the endothelium dependant relaxation to acetylcholine. Different sensitivities of smooth muscle to EDRF (possibly due to the guanylate cyclase) may explain in part the heterogeneity in endothelium-dependant responses between arteries and veins. Because EDRF does not induce changes in the spontaneous electrical and mechanical activity of portal vein it very probably does not possess calcium entry blocking properties.
THROMBOSIS RESEARCH
ZRTERIES, VEINS AND ENDOTHELIUM-DEPENDANT EFFECTS. M. FELETOU, FONDAX Groupe de Recherches Servier, FRANCE
Suppl.
VII,
RELAXATION
: CELLULAR
7 rue Amp&e
92800 Puteaux
1987
designed to determine the cellular mechanism underlying the Experiments were differences in endotheliumdependant responses to acetylcholine between arteries and veins. Using bioassay and electrophysiological techniques, the effect of endotheliumdependant relaxing factor (EDRF) released from the canine femoral artery of the dog was artery of the dog, the aorta of the compared in various vessels ; namely : the coronary rat, and the portal veins of both species. During bioassay experiments, the EDRF released under basal condition and during exposure to acetylcholine induced comparable relaxations of the canine coronary artery and rat aorta (aproximatively 35 %, for the basal release, and 75 %, for the stimulated release, of the contraction induced respectively by prostaglandin F2Q! and phenylephrine). spontaneous contractions were In contrast neither the canine nor the rat portal vein influenced by EDRF. Similarly EDRF was without effect on the portal veins contracted with phenylephrine. EDRF induced transient hyperpolarization of the canine coronary artery (average 11 mv). Neither the relaxation nor the hyperpolarization were sensitive to indomethacin excluding the intervention of prostanoids. However ouabain and potassium-free solution prevented the hyperpolarization but failed to abolish the relaxation of the canine coronary artery. Return to control solution (5.9 mMK+) after incubation in potassium free solution caused relaxation and hyperpolarization (average 17 mv) which demonstrates the existence of a sodium-potassium pump on this tissue. EDRF did not induce changes either in the membrane potential or the amplitude or the frequency of the spikes of the rat portal vein.
After contraction with prostglandin F2a ,sodium nitroprusside induced full relaxation of abolish the the canine coronary artery (ED50 = - 7.42 + 0.24) but failed to completely spontaneous activity of the rat portal vein (ED50 : - 5.03 + 0.3). So sodium nitroprusside was 250 times more effective on canine coronary artery than on rat portal vein. These experiments suggest that EDRF is not species specific as canine coronary artery and rat aorta behave identically. EDRF induces hyperpolarization of vascular smooth muscle of canine coronary artery probably by activating the Na+,K+ pump but this effect only partially explain the endothelium dependant relaxation to acetylcholine. Different sensitivities of smooth muscle to EDRF (possibly due to the guanylate cyclase) may explain in part the heterogeneity in endothelium-dependant responses between arteries and veins. Because EDRF does not induce changes in the spontaneous electrical and mechanical activity of portal vein it very probably does not possess calcium entry blocking properties.