© 1999 American Heart Association, Inc.
Rapid Communication |
Enhanced Release of Prostaglandins Contributes to Flow-Induced Arteriolar Dilation in eNOS Knockout Mice
From the Departments of Physiology (D.S., A.H., A.K., G.K.) and Pathology (C.J. Smith, C.J. Stackpole, J.A.C.), New York Medical College, Valhalla, NY; Division of Hypertension and Vascular Research (E.G.S.), Henry Ford Hospital, Detroit, Mich.
Correspondence to Gabor Kaley, PhD, Department of Physiology, New York Medical College, Valhalla, NY 10595.
Abstract—Nitric oxide and
prostaglandins were shown to contribute to the
endothelial mediation of flow-induced dilation of
skeletal muscle arterioles of rats. Thus, we hypothesized that
flow-induced dilation and its mediation are altered in gracilis muscle
arterioles of mice deficient in the gene for
endothelial nitric oxide synthase (eNOS-KO) compared
with control wild-type (WT) mice. Gracilis muscle arterioles
(
80 µm) of male mice were isolated, then cannulated and
pressurized in a vessel chamber. The increases in diameter elicited by
increases in perfusate flow from 0 to 10 µL/min were similar
in arterioles from eNOS-KO (n=28) and WT (n=22) mice (20 µm
at 10 µL/min flow). Removal of the endothelium
eliminated flow-induced dilations in vessels of both strains of mice.
N
-nitro-L-arginine (L-NNA,
10-4 mol/L) significantly inhibited flow-induced dilation
in arterioles of WT mice by 51% but had no effect on responses of
arterioles from eNOS-KO mice. Indomethacin (INDO,
10-5 mol/L) inhibited flow-induced dilation of WT mice by
49%, whereas it completely abolished this response in arterioles of
eNOS-KO mice. Simultaneous administration of INDO and L-NNA
eliminated flow-induced responses in arterioles of WT mice. Dilations
to carbaprostacyclin were similar at concentrations of
10-8 and 3x10-8 mol/L but decreased
significantly at 10-7 mol/L in arterioles of eNOS-KO
compared with those of WT mice. These findings demonstrate that,
despite the lack of nitric oxide mediation, flow-induced dilation is
close to normal in arterioles of eNOS-KO mice because of an enhanced
release of endothelial dilator
prostaglandins and suggest that this vascular adaptation
may contribute to the regulation of peripheral resistance
in eNOS-KO mice.
Key Words: transgenic mice • intraluminal flow • endothelium • nitric oxide • prostacyclin
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