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(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

Akos Koller; An Huang

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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