Vascular responses to neuropeptide Y are greater in female than male rats.

Sex differences in vascular effects of neuropeptide Y (NPY) were investigated in isolated tail artery ring segments from male and female F344 rats. Both pre- and postjunctional effects of NPY appeared to be greater in females. NPY potentiated contractions elicited by transmural adrenergic nerve stimulation (TNS), consistent with an effect on smooth muscle Y1 receptors. The degree of potentiation was significantly greater in arteries from females than males. Ovariectomy of the females resulted in a decrease in potentiation, while orchiectomy of the males resulted in an enhanced NPY effect. When NPY potentiation was measured in the presence of peptidase inhibitors, the effect of exogenous NPY was enhanced; however the enhancement was greater in arteries from females than either males or ovariectomized females. Possible male-female differences in inhibitory prejunctional Y2 receptor function were addressed using the selective agonist NPY13-36. At a low frequency of stimulation (0.5 Hz), NPY13-36 inhibited the response to TNS in arteries from females and castrated males; however, NPY13-36 had no significant effect on responses to TNS in arteries from males or ovariectomized females. Thus gonadal hormones appear to modulate several components involved in NPY neurotransmission, including tissue peptidase activity, postjunctional Y1 and prejunctional Y2 receptors. These effects may contribute to significant differences observed in vascular reactivity between females and males.