© 1998 American Heart Association, Inc.
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Superoxide Released to High Intra-arteriolar Pressure Reduces Nitric Oxide–Mediated Shear Stress– and Agonist-Induced Dilations
From the Department of Physiology, New York Medical College, Valhalla, NY.
Correspondence to Akos Koller, MD, PhD, Department of Physiology, New York Medical College, Valhalla, NY 10595.
Abstract
Abstract—It is thought that
elevated levels of reactive oxygen metabolites contribute to the
dysfunction of vascular endothelium in hypertension. We
hypothesized that high intravascular pressure itself elicits
production of superoxide, which then interferes with nitric
oxide (NO)–mediated responses of arterioles. Thus, isolated arterioles
(
80 µm in diameter) from gracilis muscle of normotensive
Wistar rats were cannulated and exposed to 140 mm Hg perfusion
pressure for 30 minutes (in the absence of perfusate flow).
After high intravascular pressure treatment, dilations to increases in
perfusate flow (0 to 30 µL/min) were significantly reduced
(from 39±2.2 to 19±2.1 µm at 30 µL/min), eliciting an
increase in wall shear stress from 20 to 60 dyne/cm2.
N
-nitro-L-arginine (10-4 mol/L)
did not affect, whereas indomethacin eliminated,
flow-induced dilations after pressure treatment. In control, substance
P (SP, 10-9 to 5x10-8 mol/L), sodium
nitroprusside (SNP, 10-8 to 10-6 mol/L), and
adenosine (ADO, 10-6 to 5x10-5
mol/L) elicited dilations (SP: 31.5±1.9 µm, SNP: 45.6±4
µm, and ADO: 37.2±4.1 µm, at maximum concentrations,
respectively). After pressure treatment, maximum dilations to SP and
SNP were significantly reduced (by 49% and 39%, respectively),
whereas responses to ADO were not affected. Presence of superoxide
dismutase (120 U/mL) and catalase (80 U/mL), but not catalase alone, in
the perfusate solution prevented the reduction in dilation of
arterioles to flow and agonists after pressure treatment by restoring
NO mediation. We conclude that high intravascular pressure per se
elicits the release of superoxide, which then interferes with NO, a
mechanism that contributes to the elevation of wall shear stress and
peripheral resistance in hypertension.
Key Words: intravascular pressure • hypertension • reactive oxygen metabolites • wall shear stress • microcirculation
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