(Hypertension. 1999;34:1073-1079.)
© 1999 American Heart Association, Inc.
Scientific Contributions |
Development of Nitric Oxide and Prostaglandin Mediation of Shear Stress–Induced Arteriolar Dilation With Aging and Hypertension
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. E-mail akos koller{at}nymc.edukoller@nymc.edu
Abstract—We hypothesized that
during hypertension, the impairment of mediation of shear
stress–induced dilation by nitric oxide (NO) is due to the prevailing
hemodynamic forces, and that mediation of this response
by NO should still be present in young spontaneously hypertensive
rats (SHR). Thus, responses to increases in perfusate flow
eliciting increases in wall shear stress were investigated in
pressurized (80 mm Hg), isolated arterioles (
70 to 100
µm) of the left or right gracilis muscle obtained from the same WKY
and SHR at 4 and 12 weeks of age. Flow-induced dilations were similar
in WKY and SHR at 4 weeks (maximum, 26.5±1.8 and 24.2±2.0 µm,
respectively). Also, the middle of the upward portion of the shear
stress–diameter curves was similar in arterioles of the 2 strains.
Inhibition of NO synthase with
N
-nitro-L-arginine (L-NNA) or
inhibition of synthesis of prostaglandins (PGs) with
indomethacin elicited an 50% reduction in
flow-dependent dilation, whereas their combined administration
eliminated the responses in both groups. In arterioles of 12-week-old
WKY, flow-induced dilation became significantly greater (maximum,
46.1±2.3 µm) than responses of arterioles of 4-week-old WKY and
12-week-old SHR (maximum, 18.3±5.9 µm), which shifted only the
shear stress–diameter curve of the 12-week-old WKY significantly to
the left. Also, at 12 weeks of age, flow-dependent dilation of
arterioles from SHR is mediated solely by PGs. Thus, shear
stress–induced arteriolar dilation is mediated by NO and PGs in
4-week-old WKY and SHR. With aging, the release of NO and PGs increases
in normotensive rats, whereas the contribution of NO to the regulation
of shear stress disappears in 12-week-old SHR, which suggests that this
change is probably caused by the increase in intraluminal pressure as
hypertension develops.
Key Words: arterioles • dilation • nitric oxide • prostaglandin • age • rats, inbred SHR • wall shear stress
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