Estrogen ameliorates N ^ω -nitro-L-arginine methyl ester-induced blood pressure increment in male spontaneously hypertensive rats: The role of cGMP

Estrogen (17beta-estradiol, or E ₂ ) reduces systolic blood pressure (SBP) increment and increases aortic cyclic guanosine monophosphate (cGMP) in male spontaneously hypertensive rats (SHRs). It is unknown, however, whether the E ₂ -enhanced aortic cGMP is essential for the BP-lowering effect or not. N ^ω -nitro-L-arginine-methyl ester (L-NAME), an L-arginine analogue and nitric oxide (NO) synthase inhibitor, significantly increases SBP and decreases aortic cGMP in male SHRs. We thus treated male SHRs with vehicle (corn oil) or E ₂ (s.c, 2 mg/kg/week) with or without L-NAME (20 mg/dl in the drinking water). SBP was measured weekly. Plasma nitrate/nitrite (NOx) concentrations and aortic cGMP levels were all measured at the end of the study. We found that SBP increment was significantly higher in L-NAME group, compared with the controls, and that E ₂ treatment reduced this L-NAME effect. Plasma NOx concentrations were not significantly different among different groups. Basal and acetylcholine-induced aortic cGMP, but not sodium nitroprusside-induced cGMP, were significantly lower in L-NAME group, compared with the controls. E ₂ co-administration did not modify L-NAME-induced aortic cGMP decrease. These data indicate that E ₂ -induced BP-lowering effect in L-NAME treated male SHRs is not closely associated with the enhancement of vascular cGMP.