Estrogen maintains nitric oxide synthesis in arterioles of female hypertensive rats.

ABSTRACT

We hypothesized that in female spontaneously hypertensive rats (SHR), estrogen moderates the dysfunction of arterioles by preserving nitric oxide synthesis. To this end, we conducted experiments on isolated gracilis muscle arterioles (approximately 55 microns in diameter) of 12-week-old (SHR divided into four groups females (fSHR), ovariectomized females (fSHR-OV), ovariectomized females with estrogen replacement (fSHR-OV+ES, 50 micrograms/kg SC 17 beta-estradiol benzoate every 48 hours), and males (mSHR). Arteriolar diameter in the presence of perfusion pressures of 60, 80, 100, and 120 mm Hg were obtained, and diameter changes were measured (at 80 mm Hg) in response to various concentrations of substance P (10(-9) to 5 x 10(-8) mol/L), sodium nitroprusside (10(-8) to 10(-6) mol/L), and A23187 (5 x 10(-8) to 10(-6) mol/L). The pressure-induced diameter of mSHR and fSHR-OV arterioles was significantly less (by approximately 10%) than that of fSHR and fSHR-OV+ES arterioles. N omega-nitro-L-arginine (10(-4) mol/L), a nitric oxide synthase inhibitor, elicited a significant decrease in basal arteriolar diameter of fSHR (by approximately 19%) and fSHR-OV+ES (by approximately 17%), thereby eliminating the differences in tone among the various groups. Dilations of fSHR and fSHR-OV+ES arterioles to substance P were significantly greater (by 140% at a concentration of 5 x 10(-8) mol/L) than those of mSHR and fSHR-OV arterioles, whereas dilations to sodium nitroprusside were not different among the groups. A23187 (a nitric oxide releaser) elicited dilations in arterioles of fSHR (5.9 +/- 1.5%, 13.0 +/- 1.8%, and 19.2 +/- 2.1%) and fSHR-OV+ES (4.3 +/- 1.0%, 10.3 +/- 2.4%, and 15.0 +/- 4.0%) but constrictions in those of mSHR (-7.5 +/- 1.6%, -25.3 +/- 39%, and -36.9 +/- 4.1%) and fSHR-OV (-2.6 +/- 1.7%, 7.4 +/- 3.3%, and -11.5 +/- 6.1%). We conclude that estrogen in fSHR is responsible for the preservation of nitric oxide synthesis in skeletal muscle arterioles, resulting in a greater modulation of pressure-induced myogenic tone than in mSHR and maintenance of nitric oxide-mediated dilations.