Abstract

and specific aims): Since the discovery of natriuretic peptides in 1981, a tremendous amount of research has characterized the molecular biology, pharmacology, and physiologic significance of this family of peptides. At the present time, 3 main NPs are known to exist; atrial (ANP), brain (BNP) and C-type natriuretic peptides (CNP). Three NP receptors have also been characterized, the A and B receptors that are linked to particulate guanylate cyclase, and the C-receptor that is thought to serve mainly a clearance function. The peptides are thought to play a role in blood pressure and fluid homeostasis. In recent years, considerable evidence has also accrued to support the hypothesis that ANP plays a physiologic role in the regulation of pulmonary vascular tone and remodeling by ANP. This project aims to further investigate the role and mechanisms of action of the NPs and their receptors in the regulation of pulmonary vascular tone and remodeling.
The specific aims are to: 1) assess the physiologic significance of NPs in modulating chronic pulmonary hypertension; 2) evaluate the mechanisms contributing to the synthesis and release of CNP and the potential physiologic role of CNP in the pulmonary vasculature; and 3) investigate regulation of NP receptor quantity, distribution, and recycling in the lungs.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL045050-05
Application #
2735174
Study Section
Lung Biology and Pathology Study Section (LBPA)
Project Start
1991-05-01
Project End
2001-06-30
Budget Start
1998-07-01
Budget End
1999-06-30
Support Year
5
Fiscal Year
1998
Total Cost
Indirect Cost

  Institution

Name
Rhode Island Hospital (Providence, RI)
Department
Type
DUNS #
161202122
City
Providence
State
RI
Country
United States
Zip Code
02903

  Publications

Preston, Ioana R; Klinger, James R; Houtchens, Jeanne et al. (2002) Pulmonary edema caused by inhaled nitric oxide therapy in two patients with pulmonary hypertension associated with the CREST syndrome. Chest 121:656-9
Klinger, J R; Pietras, L; Warburton, R et al. (2001) Reduced oxygen tension increases atrial natriuretic peptide release from atrial cardiocytes. Exp Biol Med (Maywood) 226:847-53
Mehta, S; Hill, N S (2001) Noninvasive ventilation. Am J Respir Crit Care Med 163:540-77
Preston, I R; Klinger, J R; Landzberg, M J et al. (2001) Vasoresponsiveness of sarcoidosis-associated pulmonary hypertension. Chest 120:866-72
Klinger, J R; Warburton, R R; Pietras, L A et al. (1999) Genetic disruption of atrial natriuretic peptide causes pulmonary hypertension in normoxic and hypoxic mice. Am J Physiol 276:L868-74
Klinger, J R; Warburton, R R; Pietras, L et al. (1998) Brain natriuretic peptide inhibits hypoxic pulmonary hypertension in rats. J Appl Physiol 84:1646-52
Klinger, J R; Siddiq, F M; Swift, R A et al. (1998) C-type natriuretic peptide expression and pulmonary vasodilation in hypoxia-adapted rats. Am J Physiol 275:L645-52
Arjona, A A; Hsu, C A; Wrenn, D S et al. (1997) Effects of natriuretic peptides on vascular smooth-muscle cells derived from different vascular beds. Gen Pharmacol 28:387-92
Klinger, J R; Wrenn, D S; Warburton, R R et al. (1997) Atrial natriuretic peptide expression in rats with different pulmonary hypertensive responses to hypoxia. Am J Physiol 273:H411-7
Meyer, T J; Hill, N S (1994) Noninvasive positive pressure ventilation to treat respiratory failure. Ann Intern Med 120:760-70

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