Neuropeptide Y-mediated sex- and afferent-specific neurotransmissions contribute to sexual dimorphism of baroreflex afferent function

BACKGROUND: Molecular and cellular mechanisms of neuropeptide-Y (NPY)-mediated gender-difference in blood pressure (BP) regulation are largely unknown. METHODS: Baroreceptor sensitivity (BRS) was evaluated by measuring the response of BP to phenylephrine/nitroprusside. Serum NPY concentration was determined using ELISA. The mRNA and protein expression of NPY receptors were assessed in tissue and single-cell by RT-PCR, immunoblot, and immunohistochemistry. NPY was injected into the nodose while arterial pressure was monitored. Electrophysiological recordings were performed on nodose neurons from rats by patch-clamp technique. RESULTS: The BRS was higher in female than male and ovariectomized rats, while serum NPY concentration was similar among groups. The sex-difference was detected in Y(1)R, not Y(2)R protein expression, however, both were upregulated upon ovariectomy and canceled by estrogen replacement. Immunostaining confirmed Y(1)R and Y(2)R expression in myelinated and unmyelinated afferents. Single-cell PCR demonstrated that Y(1)R expression/distribution was identical between A- and C-types, whereas, expressed level of Y(2)R was ∼15 and ∼7 folds higher in Ah- and C-types than A-types despite similar distribution. Activation of Y(1)R in nodose elevated BP, while activation of Y(2)R did the opposite. Activation of Y(1)R did not alter action potential duration (APD) of A-types, but activation of Y(2)R- and Y(1)R/Y(2)R in Ah- and C-types frequency-dependently prolonged APD. N-type I(Ca) was reduced in A-, Ah- and C-types when either Y(1)R, Y(2)R, or both were activated. The sex-difference in Y(1)R expression was also observed in NTS. CONCLUSIONS: Sex- and afferent-specific expression of Neuropeptide-Y receptors in baroreflex afferent pathway may contribute to sexual-dimorphic neurocontrol of BP regulation.