Shear stress-induced release of prostaglandin H(2) 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 microm, respectively, whereas their passive diameters were 109.4+/-4.4 and 101.9+/-6.7 microm, respectively. Dilations to increases in shear stress elicited by increases in intraluminal flow (from 0 to 25 microL/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, shear stress elicits an enhanced release of PGH(2), resulting in a reduced shear stress-dependent dilation. Thus, augmented hemodynamic forces can alter the shear stress-induced synthesis of prostaglandins, which may contribute to the elevated vascular resistance in hypertension.
Huang
A
A
Department of Physiology, New York Medical College, Valhalla, NY 10595, USA.
Sun
D
D
Koller
A
A
D000818:Animals; D001160:Arterioles / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D001572:Benzofurans / Q000494:pharmacology; D019086:Bridged Bicyclo Compounds, Heterocyclic; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines / Q000494:pharmacology; D006973:Hypertension / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D044262:Prostaglandin H2; D011463:Prostaglandins H / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors / Q000378:metabolism; D044244:Receptors, Thromboxane A2, Prostaglandin H2; D013314:Stress, Mechanical; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors
D001572:Benzofurans; D019086:Bridged Bicyclo Compounds, Heterocyclic; D004791:Enzyme Inhibitors; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines; D011463:Prostaglandins H; D011982:Receptors, Prostaglandin; D044244:Receptors, Thromboxane A2, Prostaglandin H2; D044262:Prostaglandin H2; C045749:SQ 29548; D013930:Thromboxane-A Synthase; C039936:furegrelate