Shear stress-induced release of prostaglandin H2 in arterioles of hypertensive rats

The nitric oxide-mediated portion of shear stress-induced dilation of rat gracilis muscle arterioles was shown to be impaired in spontaneously hypertensive rats (SHR). Because shear stress-induced dilation is primarily mediated by endothelium-derived prostaglandins in rat cremasteric arterioles, we hypothesized that in the cremasteric vascular bed the mediation of shear stress-induced dilation by prostaglandins is altered in hypertension. At a constant intraluminal pressure of 80 mm Hg, the active diameters of isolated rat cremasteric arterioles of normotensive 30-week-old Wistar-Kyoto rats (WKY) and SHR were 58.0 +/- 3.1 and 51.7 +/- 3.6 mu m, respectively, whereas their passive diameters were 109.4 +/- 4.4 and 101.9 +/- 6.7 mu m, respectively. Dilations to increases in shear stress elicited by increases in intraluminal flow (from 0 to 25 mu L/min) were significantly less (P < 0.05) in cremasteric arterioles isolated from SHR than from WKY. Arachidonic acid (10(-5) mol/L) elicited constrictions in SHR arterioles but dilations in WKY arterioles; The prostaglandin H-2/thromboxane A(2) (PGH(2)/TxA(2)) receptor antagonist SQ 29,548 (10(-6) mol/L) significantly increased basal diameter by 11% and normalized the attenuated shear stress-induced dilation in SHR, whereas it did not affect basal diameter and arteriolar responses of WKY. Furegrelate, a specific inhibitor of TxA(2) synthase, did not affect the response in SHR. Also, SQ 29,548 reversed the arachidonic acid-induced constriction to dilation in SHR arterioles, whereas it did not affect the dilator response in WKY arterioles. Constrictions of arterioles of WKY and SHR to U46,619 (a PGH(2)/TxA(2) receptor agonist) were not different. These results demonstrate that in cremasteric arterioles of hypertensive rats, sheer stress elicits an enhanced release of PGH,, resulting in a reduced shear stress-dependent dilation. Thus, augmented hemodynamic forces can alter the sheer stress-induced synthesis of prostaglandins, which may contribute to the elevated vascular resistance in hypertension.