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-Me)-D-beta Nal-Phe-LysNH(2) (EP 50885), four hexarelin peptide analogues that induce penile erection when injected into the paraventricular nucleus of the hypothalamus of male rats, on the concentration of NO(2)(-) and NO(3)(-) in the paraventricular dialysate was studied in male rats. EP peptides (1 microg) induced penile erection and increased the concentration of NO(2)(-) and NO(3)(-) in the paraventricular dialysate. In contrast, hexarelin (1 microg) was ineffective on either penile erection or paraventricular NO(2)(-) and NO(3)(-). EP peptide-induced penile erection was prevented by the nitric oxide synthase inhibitor N(G)-nitro-l-arginine methylester given into the paraventricular nucleus (20 microg), which also reduced the concomitant increase of NO(2)(-) and NO(3)(-) concentration in the paraventricular dialysate. In contrast, the oxytocin receptor antagonist [d(CH(2))(5)Tyr(Me)(2)-Orn(8)]vasotocin (1 microg) given into the paraventricular nucleus, was ineffective on penile erection and on the NO(2)(-) and NO(3)(-) increase induced by EP peptides, despite its ability to prevent the sexual response induced by the above peptides when given into the lateral ventricles. The present results show that EP peptides induce penile erection by activating nitric oxide synthase in the paraventricular nucleus of the hypothalamus, possibly in the cell bodies of oxytocinergic neurons that control penile erection.