GENDER DIFFERENCE IN ENDOTHELIAL DYSFUNCTION IN THE AORTA OF SPONTANEOUSLY HYPERTENSIVE RATS

We investigated endothelium-dependent responses of thoracic aorta isol ated from age-matched male and female spontaneously hypertensive rats (SHR) to explore gender differences in endothelial dysfunction that ma y contribute to the sexual dimorphism observed in the development of h ypertension in this strain. Endothelium-dependent relaxation in respon se to acetylcholine (10(-9) to 10(-4) mol/L) was significantly greater in female rats than in male rats, although impaired responses were se en in both sexes compared with normotensive controls. Inhibition of cy clooxygenase by indomethacin (10(-5) mol/L) improved endothelium-depen dent relaxation, but it did not abolish the gender difference. Relaxat ions in response to sodium nitroprusside were identical in denuded aor tic rings from male and female SHR. Acetylcholine at higher concentrat ions (10(-6) to 10(-4) mol/L) induced endothelium-dependent contractio n in intact, quiescent aortic rings from male SHR but not in those fro m female SHR. After incubation with N-G-nitro-L-arginine (10(-4) mol/L ), contraction in response to acetylcholine became apparent in rings f rom female SHR, but it was still significantly less pronounced than in similarly treated rings from male SHR. Endothelium-dependent contract ion was prevented by indomethacin in both sexes, suggesting that a cyc looxygenase product such as endoperoxide may be mediating this effect. Because responses evoked by the thromboxane/endoperoxide receptor ago nist U46619 (10(-10) to 10(-6) mol/L) were not greater in rings from m ale SHR than those from female SHR, increased smooth muscle responsive ness or higher thromboxane/endoperoxide receptor density in the males could not account for the differences in endothelium-dependent contrac tion. These results suggest that sex steroid hormones may control endo thelium-dependent vascular reactivity. The less severe endothelial dys function in the female SHR can contribute to the gender differences ob served in the extent and rate of progression of hypertension in the SH R.