Role of endothelium in responses of vascular smooth muscle.

Laboratoire de Physi% Rie et Physio{Jath% Rie Cc'rchrova.l'cu/aire, I NSERM U 182, CNRS ERA 361, Unil'ersite Paris VII, Paris, alld *Lahoratoire de P/wrmac% Rie, UER Mcdecine et Pharmacie, Ullil'ersitc de LimoRcs, LimoRe.l', France Summary: The effect of endothelium removal on pial ar tery constriction in response to norepinephrine (NE) was studied in vitro using a perfused vessel setup in which pressure increases indicate vasoconstriction, In deen dothelialized rabbit arteries, the reaction to extraluminal NE was found to be characterized by a much higher E max (2,0 times) and a slight (but significant) leftward shift of the concentration-response curve (lower EC50) compared with control vessels. In cat arteries subjected to either extra-or intraluminal NE, the E max was also substantially A few years ago, Furchgott and Zawadzki (1980) showed that the presence of the endothelium was an essential condition for obtaining relaxation of rabbit thoracic aorta strips in response to acetyl choline. Since then, many studies have confirmed the essential role of the endothelium in vasodilata tions induced by various agents and in a variety of preparations [see Furchgott (1983) for review].In contrast to this burgeoning literature on dilator agents, very few reports (e.g., Cocks and Angus, 1983;Egleme et al., 1984) have appeared on con strictor agents and the influence of the endothelium, and none deal with cerebral vessels. It seemed im portant to us to determine whether vasoconstrictor responses in the cerebral circulation could be influ enced by the vascular endothelium since naturally occurring agents such as norepinephrine (NE) and serotonin are known to be released during (patho)physiological phenomena such as vaso spasm (du Boulay et aI., 1983;Cook, 1984) of any kind of lesion or alteration of the endothelial lining such as is present in atherosclerosis. In this article, we report the influence of removing the en dothelium on the response of rabbit and cat pial arteries to NE. MATERIALS AND METHODSFauve de Bourgogne rabbits or European-type cats were anesthetized and decapitated. The brain was rapidly removed and placed in a dish containing a physiological solution of the following composition (mM): NaCI 119, KCI 5, CaCl1 0.75, MgCl, 1.2, NaH,P04 1, NaHCO, 1, N-2-hydroxy e thyl piperazi n e-N-2-eth a nesulfonic acid 25; with pH adjusted to 7.4 at 20°C. This solution was pre ferred to a bicarbonate-buffered Krebs solution for the preparation since the pH was more constant (not depen dent on CO, saturation). The main branches of the middle cerebral ar t eries (MCAs) were ligated over a length of � 10 mm in the rabbit and 15 mm in the cat, starting at the circle of Willis. The endothelium of one of each pair of arteries was removed by rubbing the intimal surface with a stainless-steel tube of appropriate diameter in serted completely through the lumen. The arteries were then cannulated with a short stainless-steel tube, re moved from the brain, and placed in a 50-mt organ bath at 37°C where they were connected to a ...

Section: Dilatation Experimentsmentioning

confidence: 99%

“…Since then, many studies have confirmed the essential role of the endothelium in vasodilata tions induced by various agents and in a variety of preparations [see Furchgott (1983) for review].…”

mentioning

confidence: 99%

Pial Artery Responses to Norepinephrine Potentiated by Endothelium Removal

Sercombe

Verrecchia

Oudart

et al. 1985

“…Zawadzki (1980), a wide variety of experimental data have proved the utter importance of the vas cular endothelium in the regulation of vascular smooth muscle tone and reactivity (see Furchgott, 1983;Vanhoutte et aI., 1986;Furchgott and Van houtte, 1989). Acetylcholine and many other exog enous stimuli act upon the endothelial cells, which in turn release relaxing substances (endothelium derived relaxing factor, EDRF), leading to the re laxation of the vascular smooth muscle.…”

mentioning

confidence: 99%

Contractile and Endothelium-Dependent Dilatory Responses of Cerebral Arteries at Various Extracellular Magnesium Concentrations

Faragó

Szabó

Dóra

et al. 1991

Summary:To clarify the effect of extracellular magne sium (Mg2+) on the vascular reactivity of feline isolated middle cerebral arteries, the effects of slight alterations in the Mg2 + concentration on the contractile and endothe lium-dependent dilatory responses were investigated in vitro. The contractions, induced by 1O-8_IO-s M norepi nephrine, were significantly potentiated at low Mg2 + (0,8 mM v. the normal, 1.2 mM). High (1.6 and 2.0 mM) Mg2 + exhibited an inhibitory effect on the contractile re sponses, No significant changes, however, in the EC so values for norepinephrine were found. The endothelium dependent relaxations induced by 1O-8_10-s M acetyl choline were inhibited by high (1.6 and 2.0 mM) Mg2+. Lowering of the Mg2+ concentration to 0.8 mM or total withdrawal of this ion from the medium failed to alter the dilatory potency of acetylcholine. The changes in the dilDuring the past decade, a considerable amount of data has been generated concerning the effect of extracellular magnesium ions (Mg2 + ) on vascular smooth muscle tone and reactivity. Acute with drawal of Mg2 + elevates the basal tone of the arter ies, and contractile responses to various agonists are enhanced in Mg2+ -deficient solutions. Eleva tion of Mg2+ , however, relaxes the smooth muscle and attenuates vasoconstriction (see Altura and Al tura, 1981,1984,1985. Abbreviations used: ECso, 50% effective concentration; EDRF, endothelium-derived relaxing factor. From the original observations of Furchgott and ------------ 161atory responses also shifted the ECso values for acetyl choline to the right. The present results show that the contractile responses of the cerebral arteries are ex tremely susceptible to the changes of Mg2 + concentra tions. In response to contractile and endothelium dependent dilatory agonists, Mg2+ probably affects both the calcium influx into the endothelial and smooth muscle cells as well as the binding of acetylcholine to its endo thelial receptor. Since Mg2 + deficiency might facilitate the contractile but not the endothelium-dependent relax ant responses, the present study supports a role for Mg2 + deficiency in the development of the cerebral vasospasm.

“…, 1983;Rubani and Paul, 1985), since the cerebroarterial relaxation was par tially attenuated by treatment with cyc100xygenase inhibitors (N. To da, unpublished data). Anoxia sup presses the release of endothelium-derived relaxing factor (Furchgott, 1983), suggesting that the release of this substance is not involved.…”

Section: Discussionmentioning

confidence: 99%

Reoxygenation and Calcium-Induced Cerebroarterial Contractions as Affected by Vasodilator Agents

Bian

Toda

1988

Summary: In helical strips of dog cerebra� arterie . s . ex posed to Ca2+ -free medium under hYPoxlc condltions (95% N 2 and 5% CO 2 ), prostaglandin (PO) F 2 1l produced a slight tonic contraction. The addition . of Ca2+ evok � d a phasic contraction followed by relax�t � on and a sus . t � med contraction, and reoxygenation ehclt � d an addltIOnal The mechanical responses of isolated cerebral ar teries to vasodilator substances differ from those of extracerebral arteries. For instance, Ca 2 + entry blockers, including verapamil, diltiazem, nifed ipine, nicardipine, and flunarizine, relax cerebral arteries more than extracerebral arteries (Shimizu et aI., 1980; Van Nueten and Vanhoutte, 1981; Ya mamoto et aI., 1983), whereas relaxations caused by acetylcholine and isoproterenol are not so evi dent in cerebral arteries as in others (Toda, 1974a(Toda, , 1979. Prostaglandin (PG) 1 2 , nitroglycerin, and Ca 2 + entry blockers produce marked relaxations of cerebral arteries; however, their mechanisms of ac tion are quite different. PGI 2 and nitroglycerin relax the arteries, possibly by accumulation of cellular cyclic AMP and cyclic GMP, respectively (Kuko-