Effect of VPAC2 agonist on improving cardiac output in pulmonary hypertension

Abstract

Pulmonary hypertension (PH) is associated with significant perioperative risk for major complications, including cardiac arrest and death. Vasoactive intestinal peptide (VIP) and its related peptide PACAP are known to have vasodilatory and protective effects in several organs and VIP has been expected to be promising treatment option for PH. However, still little is known about the role of VIP/PACAP signaling in PH. Previously we presented that decreased expression of VIP and PACAP were associated with increased their receptors VPAC1, VPAC2, and PAC1 in monocrotaline‐induced PH. These data raised the question that altered expression of the receptors could increase vasodilatory response of pulmonary artery to VIP/PACAP and may contribute to improving cardiac performance in PH To answer the question, we investigated effect of administration of VIP/PACAP agonists on pulmonary/systemic pressure, the vascular resistances and cardiac output in monocrotaline‐induced PH. VPAC2 but not VPAC1, PAC1agonist decreased pulmonary arterial pressure and its vascular resistance and improved cardiac output, almost as same as prostacyclin in the PH rats, while not affecting pulmonary circulation in normal rats. Therefore, increased VPAC2 expression may be involved in enhanced vasodilatory responses and contribute to improved cardiac output. VPAC2 agonist may be a promising treatment for PH.