Submitted on December 4, 2006
Accepted on July 2, 2007
Functional arginine-vasopressin system in early heart maturation
Jolanta Gutkowska1*, Malgorzata Miszkurka1, Bogdan Danalache1, Natig Gassanov2, Dongaho Wang1, and Marek Jankowski1
1 Laboratoire de biochimie cardiovasculaire, Centre hospitalier de l'Universite de Montreal (CHUM Hotel-Dieu), Montreal, Canada
2 Department of Internal Medicine III, University of Cologne, Cologne, Germany; Laboratoire de biochimie cardiovasculaire, Centre hospitalier de l'Universite de Montreal, Montreal, Canada
* To whom correspondence should be addressed. E-mail: jolanta.gutkowska{at}umontreal.ca.
Since the neurohypophyseal hormone 8-arginine-vasopressin (AVP) is involved in cardiovascular tissue hypertrophy and myocyte differentiation, it is possible that local AVP plays a role in heart maturation. AVP-specific radioimmunoassay, reverse transcription-polymerase chain reaction and immunoblotting measuring AVP receptors (VR) were used to investigate heart tissues from newborn and adult rats. To test AVP's role in differentiation and specialization into ventricle-like cardiomyocytes, we studied GFP-P19Cl6 stem cells holding green fluorescence protein (GFP) driven by the myosin light chain-2v (MLC-2v) promoter. VR1 transcripts and proteins were higher in adult than in newborn rat hearts. In contrast, VR2 increased from postnatal days 1 to 5, and was barely detected in the adult rat heart. In cardiomyocytes expressing troponin C, immunofluorescence revealed VR2 and VR1. Intracellular cAMP increased 6.5-fold and 8.9-fold in response to the selective VR2 agonist 1-desamino-8-D-AVP (DDAVP), after 1- and 24-h treatments, respectively. Cardiac AVP was high in 1-day-old rats (330 ± 26 pg/mg protein) and in 5-day-old rats (276 ± 53 pg/mg protein) but low (98 ± 15 pg/mg protein) in 66-day-old rats. AVP immunostaining was detected in the tunica adventitia and endothelium of the coronary vessels. The possible role of AVP in cardiomyogenesis was indicated by DDAVP-AVP-dependent differentiation of GFP-P19Cl6 stem cells into contracting cells displaying GATA4, a cardiac-specific marker, and ventricle-specific MLC. Together, it is suggested that the AVP system is implicated in postnatal cardiac maturation.
