Cardioprotective role of the VIP signaling system.

Vasoactive intestinal peptide (VIP) is a 28-amino acid peptide that belongs to a family of structurally related peptide hormones including pituitary adenylate cyclase-activating peptide (PACAP). These hormones are widely distributed in the nervous system, where they act as neurotransmitters. Their biological effects are mediated by specific receptors, VPAC1 and VPAC2, which have comparable affinity for VIP and PACAP, and PAC1, which binds VIP with 1,000-fold lower affinity than PACAP. Both peptides are involved in autonomic regulation of the cardiovascular system, where they exert positive inotropic and chronotropic effects, and cause coronary vasodilatation. Additionally, PACAP inhibits proliferation of cardiac fibroblasts. Several cardiovascular diseases, such as myocardial fibrosis, heart failure, cardiomyopathy and pulmonary hypertension, have been found to be associated with changes in myocardial VIP concentration or with alteration of affinity, density and physiological responsiveness of VIP/PACAP receptors. Application of the peptides or their agonists has beneficial effect in hypertension, heart failure and myocardial fibrosis. Taken together, VIP and PACAP have beneficial effects in various pathological conditions.