Role of calcitonin gene-related peptide (CGRP) in chronic hypoxia-induced pulmonary hypertension in the mouse. Influence of gene transfer in vivo.
Calcitonin gene-related peptide (CGRP) is believed to play an important role in maintaining low pulmonary vascular resistance (PVR) and may be involved in modulating the pulmonary vascular response to chronic hypoxia. In the present study, an adenoviral vector encoding CGRP (AdRSVCGRP) was used to examine the effects of in vivo gene transfer of CGRP to the lung on increases in PVR, right ventricular mass, and pulmonary vascular remodeling that occurs in chronic hypoxia in the mouse. Following intratracheal administration of AdRSVCGRP or reporter gene mice were exposed to 16 days of chronic hypoxia (FIO(2) 0.10). The increase in pulmonary arterial pressure (PAP), PVR, right ventricular mass, and pulmonary vascular remodeling in response to chronic hypoxia was attenuated in animals overexpressing CGRP, whereas systemic arterial pressure was not altered. Following exposure to hypoxia, a subgroup of mice were treated with capsaicin, which did not significantly alter CGRP expression in the mouse lung. These data show that in vivo transfer of the CGRP gene to the lung attenuates the increase in PVR, right ventricular mass, and pulmonary vascular remodeling in chronically hypoxic mice with little effect on the systemic circulation. Moreover, these data suggest that adenoviral gene transfer of CGRP to the lung results in expression of the gene product in non-neural tissue.
Bivalacqua
Trinity J
TJ
Department of Pharmacology, Tulane University School of Medicine, New Orleans, LA 70112, USA.
Hyman
Albert L
AL
Kadowitz
Philip J
PJ
Paolocci
Nazareno
N
Kass
David A
DA
Champion
Hunter C
HC
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000502:physiology*; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology*; D006976:Hypertension, Pulmonary / Q000503:physiopathology*; D000860:Hypoxia / Q000150:complications / Q000503:physiopathology*; D051379:Mice; D011652:Pulmonary Circulation / Q000187:drug effects / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology; D014162:Transfection
D011994:Recombinant Proteins; D015740:Calcitonin Gene-Related Peptide