Androgen-receptor defect abolishes sex differences in nitric oxide and reactivity to vasopressin in rat aorta

Contractions of rat thoracic aorta to vasopressin WP) are threefold higher in females (F) than in males (M), primarily because nitric oxide (NO) atten uation of contraction is greater in M. To determine the role of the androge n receptor (AR) in this mechanism, vascular reactivity to VP was examined i n thoracic aorta of the testicular-feminized male (Tfm) rat, which has an X -linked, recessive defect in AR function in affected M. Maximal contraction of normal aortas to VP was fourfold higher in F (4,128 +/- 291 mg/mg ring wt) than in M (971 +/- 133 mg); maximal response of Tfm (3,967 +/- 253 mg) was similar to that of normal F. N-G-nitro-L-arginine methyl ester increase d maximal response to VP threefold in M but had no effect in F or Tfm. In c ontrast, maximal contraction of normal aortas to phenylephrine was 43% high er in M (4,011 +/- 179 mg) than in F (2,809 +/- 78 mg); maximal response of Tfm (2,716 +/- 126 mg) was similar to that of normal F. N-G-nitro-L-argini ne methyl ester increased maximal response to phenylephrine by >50% in F an d Tfm but had no effect in M. Maximal contractile response to 80 mM KCl did not differ among M, F, or Tfm. Thus androgens and normal vascular AR funct ion are important in the greater NO-mediated attenuation of reactivity to V P in M than in F rat aorta, which may involve specific modulation of endoth elial VP signal transduction pathways and NO release by androgens. These da ta also establish the importance of the Tfm rat as a model to study the eff ects of androgens on cardiovascular function.