(Hypertension. 2000;36:856.)
© 2000 American Heart Association, Inc.
Scientific Contributions |
Endothelin and Prostaglandin H2/Thromboxane A2 Enhance Myogenic Constriction in Hypertension by Increasing Ca2+ Sensitivity of Arteriolar Smooth Muscle
From the Institute of Pathophysiology (Z.U., A.K.), Semmelweis University of Medicine, Budapest, Hungary, and the Department of Physiology (Z.U., A.K.), New York Medical College, Valhalla, NY.
Correspondence to Akos Koller, MD, PhD, Department of Physiology, New York Medical College, Valhalla, NY 10595. E-mail koller{at}nymc.edu
Abstract—The myogenic response of
skeletal muscle arterioles is enhanced in hypertension because of the
release of endothelin (ET) and prostaglandin H2
(PGH2)/thromboxane A2
(TxA2) from the endothelium. We
hypothesized that ET and PGH2/TxA2 modulate
Ca2+ signaling in arteriolar smooth muscle and thereby
enhance myogenic constriction. Thus, simultaneous changes
in intracellular Ca2+ concentration in smooth muscle
([Ca2+]i), measured by fura 2
microfluorometry (expressed as Ca2+ fluorescence
ratio [RCa]), and diameter were obtained as a function of
intraluminal pressure (Pi) in isolated cannulated gracilis
muscle arterioles (diameter 
120 µm) of normotensive Wistar
rats (WR) and spontaneously hypertensive rats (SHR). In the absence of
extracellular Ca2+, increases in Pi from 20 to
160 mm Hg increased the passive diameter of arterioles without
changes in RCa. In the presence of extracellular
Ca2+ and endothelium, increases in
Pi elicited similar increases in RCa (30±7%
for control and 33±8% for SHR at 160 mm Hg) but a significantly
(P<0.05) greater constriction of SHR arterioles
compared with WR arterioles (at 160 mm Hg, 55±4% versus
38±2%, respectively, of passive diameter). In the absence of the
endothelium, Pi-induced changes in the
RCa and diameter of SHR and WR arterioles did not differ
significantly. Also, a step increase in Pi (from 80 to
140 mm Hg) elicited a similar increase in RCa but
greater constrictions in SHR versus WR arterioles. In the presence of
the TxA2 receptor inhibitor SQ29,548 and the
ETA receptor inhibitor BQ123, there was no
difference between responses of SHR and WR arterioles. In WR
arterioles, increasing concentrations of KCl elicited a significant
increase in RCa (38±7% at 80 mmol/L) and completely
constricted the arterioles. In contrast, constrictions to ET (52±7%
at 3x10-12 mol/L) and the TxA2
agonist U46619 (40±8% at 3x10-9 mol/L) were
not accompanied by increases in RCa at submaximal
concentrations. Collectively, these findings suggest that in
hypertension, endothelium-derived ET and
PGH2/TxA2 increase the Ca2+
sensitivity of the contractile apparatus of arteriolar
smooth muscle; thus, the similar increases in
[Ca2+]i in response to the elevation of
intraluminal pressure elicit greater myogenic constriction.
Key Words: hypertension, experimental • endothelium • thromboxanes • endothelin • calcium
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