Penile erection induced by EP 80661 and other hexarelin peptide analogues:involvement of paraventricular nitric oxide

The effect of GAB-D-Trp(2-Me)-D-Trp(2-Me)-LysNH(2) (EP 80661), GAB-D-Trp(2- Me)-D-Trp(2-Me)-D-Trp(2-Me)-LysNH(2) (EP 60761), GAB-D-Trp(2-Me)-LysNH(2) ( EP 91071) and GAB-D-Trp(2-Mr)-D-beta Nal-Phe-LysNH(2) (EP 50885), four hexa relin peptide analogues that induce penile erection when injected into the paraventricular nucleus of the hypothalamus of male rats. on the concentrat ion of NO2- and NO3- in the paraventricular dialysate was studied in male r ats. EP peptides (1 mug) induced penile erection and increased the concentr ation of NO2- and NO3- in the paraventricular dialysate. In contrast, hexar elin (1 mug) was ineffective on either penile erection or paraventricular N O2- and NO3-. EP peptide-induced penile erection was prevented by the nitri c oxide synthase inhibitor N-G-nitro-1-arginine methylester given into the paraventricular nucleus (20 mug). which also reduced the concomitant increa se of NO2- and NO3- concentration in the paraventricular dialysate. In cont rast, the oxytocin receptor antagonist [d(CH2)(5)Tyr(Me)(2)-Orn(8)]vasotoci n (1 mug) given into the paraventricular nucleus, was ineffective on penile erection and on the NO2- and NO3- increase induced by EP peptides, despite its ability to prevent the sexual response induced by the above peptides w hen given into the lateral ventricles. The present results show that EP pep tides induct penile erection by activating nitric oxide synthase in the par aventricular nucleus of the hypothalamus, possibly in the cell bodies of ox ytocinergic neurons that control penile erection. (C) 2001 Elsevier Science B.V. All rights reserved.