Affiliation:
1. From the Institut de Cardiologie de Montréal, Centre de Recherche (E.T., T.-D.N.), Montreal, and Département de Neurochirurgie, Hôpital Notre-Dame, Montréal, Canada.
Abstract
Background and Purpose
—Endothelin-1 (ET) has been shown to be involved in human pathological conditions, but its physiological function remains to be elucidated. The aim of this work was to assess whether endothelium-derived ET was involved in the overall responsiveness of freshly isolated human pial arteries.
Methods
—Samples of cerebral cortex, otherwise discarded, were obtained during tumor or epileptic lesion resections (n=10 donors). Arterial segments were isolated and mounted on a microvessel myograph.
Results
—Inhibition of nitric oxide (NO) formation with
N
ω
-nitro-
l-
arginine (L-NA, 100 μmol/L) increased basal tone by 7±1%E
max
(n=5). This increase in tone was fully abolished in the presence of BQ123 (1 μmol/L; ET
A
receptor antagonist,
P
<.05) but potentiated by a subthreshold concentration of exogenous ET (1 nmol/L; 33±8%E
max
;
P
<.05). In the presence of L-NA, serotonin (10 μmol/L)–induced tone was doubled compared with the control response (
P
<.05) but reduced by 90% in the presence of BQ123 (
P
<.05). In the absence of L-NA, BQ123 prevented serotonin-induced tone (n=3). Oxymetazoline, a selective α
2
-adrenergic receptor agonist, induced an endothelium-dependent relaxation of preconstricted human pial arteries. The relaxation was partially sensitive to NO synthase inhibition and fully prevented by the addition of ET, whereas substance P–induced relaxation was preserved. Glibenclamide (1 μmol/L), an inhibitor of ATP-sensitive K
+
channels and tetraethylammonium (1 mmol/L), an inhibitor of Ca
2+
-activated K
+
channels had no effect on oxymetazoline-induced relaxation.
Conclusions
—The results of this study suggest first that ET is involved in the tonic response induced by NO synthase inhibition; second, part of the contractile response induced by serotonin is endothelium-dependent and sensitive to BQ123; and third, the data suggest that activation of α
2
-adrenergic receptors generated an endothelium-dependent relaxation that was selectively inhibited by exogenous ET.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Advanced and Specialized Nursing,Cardiology and Cardiovascular Medicine,Neurology (clinical)
Cited by
51 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献