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.
Correspondence to Eric Thorin, Institute de Cardiologie de Montréal, Centre de Recherche, 5000 rue Belanger Est, Montréal (PQ) H1T 1C8, Canada. E-mail thorin{at}icm.umontreal.ca
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
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
Department
of Internal Medicine,
Cardiovascular Division,
University of Iowa College of Medicine,
Iowa City, Iowa
© 1998 American Heart Association, Inc.
Original Contributions
Control of Vascular Tone by Endogenous Endothelin-1 in Human Pial Arteries
-nitro-L-arginine (L-NA,
100 µmol/L) increased basal tone by 7±1%Emax
(n=5). This increase in tone was fully abolished in the presence of
BQ123 (1 µmol/L; ETA receptor
antagonist, P<.05) but potentiated by a
subthreshold concentration of exogenous ET (1 nmol/L;
33±8%Emax; 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 
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 Ca2+-activated
K+ channels had no effect on oxymetazoline-induced
relaxation. 2-adrenergic receptors generated an
endothelium-dependent relaxation that was selectively
inhibited by exogenous ET.
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