Expression of vasoactive intestinal peptide and related receptors in overcirculation-induced pulmonary hypertension in piglets.
The pathobiology of pulmonary arterial hypertension (PAH) is not understood completely. Recent observations in patients with PAH and in knockout models have raised the idea that a defect in vasoactive intestinal peptide (VIP) may be involved in PAH physiopathology. Therefore, we investigated the expressions of VIP, the related pituitary adenylate cyclase-activating polypeptide (PACAP), and their receptors (VPAC1, VPAC2, and PAC1) in piglets with overcirculation-induced pulmonary hypertension as an early-stage PAH model. Seventeen piglets were randomized to an anastomosis between the innominate and the main pulmonary artery, or to a sham operation. After 3 mo, a hemodynamic evaluation was performed and the lung tissue was sampled for biologic and histologic studies. The shunting increased pulmonary vascular resistance (PVR) by 100% and arteriolar medial thickness by 85%. VIP and VPAC1 gene expressions were decreased and increased, respectively. VPAC1 gene expression was positively correlated to PVR. VPAC2 and PAC1 immunoreactivity was seen in pulmonary arterial smooth muscle. VIP and PACAP immunostaining was observed in nerve fibers surrounding the pulmonary arterial smooth muscle. In conclusion, overcirculation-induced pulmonary hypertension is accompanied by a down-regulation of VIP signaling, without change in PACAP expression. These results are consistent with the notion that abnormal VIP signaling takes part in PAH pathogenesis.
Vuckovic
Aline
A
Laboratory of Physiology and Physiopathology, Université Libre de Bruxelles, B-1070 Brussels, Belgium. avuckovi@ulb.ac.be
Rondelet
Benoît
B
Brion
Jean-Pierre
JP
Naeije
Robert
R
D000818:Animals; D006439:Hemodynamics; D006801:Humans; D006976:Hypertension, Pulmonary / Q000503:physiopathology*; D008168:Lung / Q000378:metabolism; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051239:Receptors, Vasoactive Intestinal Peptide, Type II / Q000235:genetics / Q000378:metabolism; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D013552:Swine; D014660:Vasoactive Intestinal Peptide / Q000235:genetics / Q000378:metabolism*
D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D012333:RNA, Messenger; D051239:Receptors, Vasoactive Intestinal Peptide, Type II; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I; D014660:Vasoactive Intestinal Peptide