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In This Journal ScanPediatric ResearchChestCirculation ResearchThe New England Journal of Medicine

Pulmonary Hypertension, February 2006 Journal Scan

FromChestFebruary 2006  ( Volume 129, Number 2 )

Pulmonary Hemodynamic Responses to Brain Natriuretic Peptide and Sildenafil in Patients With Pulmonary Arterial HypertensionKlinger JR, Thaker S, Houtchens J, Preston IR, Hill NS, Farber HW 
Chest.  2006;129(2):417-425

Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are proteins that are expressed in the heart.[1] These peptides raise the intracellular cyclic guanosine monophosphate (cGMP) levels to cause vasorelaxation. Another benefit of these peptides is the inhibition of vascular smooth muscle proliferation.[2] Study results have demonstrated inhibition of pulmonary vasoconstriction in pulmonary arterial rings by these 2 peptides[3] and the development of increased pulmonary artery pressures when the gene for encoding of ANP is disrupted.[4] The exact hemodynamic response to these peptides in patients with pulmonary arterial hypertension (PAH) has not been adequately studied, but the use of natriuretic peptides in patients with left heart disease and chronic hypoxic lung disease has demonstrated a decrease in pulmonary artery pressure (PAP).

This study looks at the effect of BNP acutely on hemodynamics (compared with inhaled nitric oxide [iNO] and epoprostenol) in patients with PAH and then the effect on hemodynamics when the pohsphodiesterase-5 (PDE-5) inhibitor sildenafil is added. This open-label study ran from September 2002 to June 2003 and enrolled 13 patients. Inclusion criteria included mean PAP (mPAP) levels > 25 mm Hg at rest, and a World Health Organization class I PAH group. They also had to be de novo patients. All patients had a Swan-Ganz catheter placed and received epoprostenol and, in addition, 8 patients also received iNO. They then received 2 infusions of the human B-type natriuretic peptide nesiritide. The second infusion of nesiritide occurred 1 hour after a single dose of oral sildenafil.

Hemodynamics were evaluated at various points during each separate drug administration. Plasma BNP levels were also obtained. mPAP was 48.6 ± 3.7 mm Hg and mean pulmonary vascular resistance (PVR) was 698 ± 105 dynes·cm/s². The resultant findings were decreased mPAP with both iNO and epoprostenol and an increase in cardiac index and decrease in PVR with epoprostenol. The BNP infusion on its own did not affect mPAP or PVR. With 1 dose of sildenafil, the mPAP and PVR did drop below baseline, and the addition of BNP after the sildenafil dose resulted in a further decline in mPAP. The decrease in mPAP and PVR in this group remained visible for up to 6 hours after stopping the BNP infusion, signifying the longest duration of response of all the groups. Only 1 patient demonstrated a vasodilator response to epoprostenol or sildenafil alone, but 4 of 12 patients demonstrated a positive vasodilator response to sildenafil with BNP.

Increased circulating BNP levels may help slow right ventricular remodeling and may even inhibit the proliferation of pulmonary vascular smooth muscle. With their effect on endothelin synthesis (inhibition), the natriuretic peptides could improve the effects of endothelin receptor antagonists. What is uncertain here is the rationale for the lack of response (decreased mPAP and PVR) to the BNP infusion alone but the positive response when sildenafil was added. The authors believe that the dose or duration of the BNP infusion may not have been adequate. Further studies are needed to determine whether there is a place for chronic BNP therapy in the treatment of PAH.ReferencesHill NS, Klinger JR, Warburton RR, et al. Brain natriuretic peptide: possible role in the modulation of hypoxic pulmonary hypertension. Am J Physiol. 1994;266:L308-L315.Hutchison HG, Trindade PT, Cunanan DB, et al. Mechanisms of natriuretic-peptide-induced growth inhibition of vascular smooth muscle cells. Cardiovasc Res. 1997;35:158-167.Klinger JR, Warburton RR, Pietras L, et al. Brain natriuretic peptide attenuates the development of pulmonary hypertension in hypoxia-adapted rats. J Appl Physiol. 1998;84:1646-1652.Klinger JR, Warburton RR, Pietras L, et al. Genetic disruption of atrial natriuretic peptide causes pulmonary hypertension in normoxic and hypoxic mice. Am J Physiol. 1999;276:L868-L874.

Abstract

This is a part of article Pulmonary Hypertension, February 2006 Taken from "Erectile Disfunction Medication" Information Blog

Labels: pharmacology

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