In rabbit tissue tests, the peptide bremelanotide (pt-141) did not relax vaginal muscle or arteries, while other neuropeptides like VIP, PACAP, and alpha‑MSH did. This suggests pt-141’s effects on female sexual arousal are probably not due to direct peripheral muscle relaxation.

Hypothalamic neuropeptides centrally modulate sexual arousal. However, the role of neuropeptides in peripheral arousal has been ignored. Vascular and non-vascular smooth muscle relaxation in the vagina is important for female sexual arousal. To date, in vitro studies have focused on vaginal strips with no studies on vaginal arteries. The aim of this study was to compare the effects of sexual hypothalamic neuropeptides on rabbit vaginal wall strips and arteries. Tissue bath and wire myography techniques were used to measure isometric tension from strips and arteries, respectively. Pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP) relaxed both preparations, effects that were only antagonized by the VIP/PACAP antagonist VIP6-28 (10 nM) and the PAC(1) antagonist PACAP 6-38 (1 microM). The melanocortin agonist alpha-melanocortin-stimulating hormone (1 microM), but not bremelanotide (1 microM), also relaxed both preparations. Oxytocin and vasopressin contracted vaginal preparations, which could be antagonized by the V(1A) antagonist SR 49059. Neuropeptide Y (NPY) and the NPY Y(1) agonist Leu(31), Pro(34) NPY only contracted arteries, which was antagonized by the NPY Y(1) receptor antagonist BIBP 3226. Melanin-concentrating hormone (MCH; 1 microM) contracted arteries. Hypothalamic neuropeptides can exert contractile and relaxant effects on vaginal strips and arteries. NPY Y(1), V(1A), MCH(1) antagonists as well as VIP/PAC(1) agonists may have therapeutic potential in both central and peripheral female sexual arousal. Differences in effect of neuropeptides between preparations raise the question of which preparation is important for female sexual arousal.