Role of calcitonin gene-related peptide (CGRP) in chronic hypoxia-induced pulmonary hypertension in the mouse: Influence of gene transfer in vivo

Trinity J. Bivalacqua, Albert L. Hyman, Philip J. Kadowitz, Nazareno Paolocci, David A. Kass, Hunter C. Champion

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

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 (FIO2 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.

Original languageEnglish (US)
Pages (from-to)129-133
Number of pages5
JournalRegulatory Peptides
Volume108
Issue number2-3
DOIs
StatePublished - Oct 15 2002

Keywords

  • CGRP
  • Pulmonary vascular bed
  • Right ventricular hypertrophy

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Endocrinology
  • Clinical Biochemistry
  • Cellular and Molecular Neuroscience

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