The natriuretic peptides and their role in disorders of right heart dysfunction and pulmonary hypertension Lok B. Yap a, * , Houman Ashrafian b , Dev Mukerjee c , John G. Coghlan d , Peter M. Timms e a Department of Cardiology, Homerton University Hospital NHS Trust, London, E9 6SR, UK b Department of Cardiology, Ealing Hospital, London, UK c Department of Rheumatology, Broomfield Hospital, Essex, UK d Department of Cardiology, Royal Free Hospital, London, UK e Department of Clinical Biochemistry, Homerton University Hospital, London, UK Received 1 December 2003; accepted 1 June 2004 Available online 2 July 2004 Abstract Atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) are increased in conditions with cardiac ventricular volume and pressure overload. The general physiological and potential therapeutic roles of natriuretic peptides in respiratory disease, right ventricular (RV) dysfunction, and pulmonary arterial hypertension (PAH) are reviewed. BNP levels can be used to differentiate between dyspneic patients with a pure respiratory defect and those with RV dysfunction. BNP levels also correlate with mean pulmonary arterial pressure (mPAP) and pulmonary vascular resistance (PVR) in patients with PAH (atrial septal defect, chronic thromboembolic disease, and scleroderma). BNP is a predictor of mortality in patients with primary pulmonary hypertension (PPH). These are important clinical implications in that a noninvasive blood test may be used to identify high-risk patients for more invasive procedures such as cardiac catheterization. BNP or NT-proBNP measurements may also be used to guide therapy (e.g., pulmonary vasorelaxants) in PAH since upregulation of the natriuretic peptide pathway has been shown to reduce cardiac hypertrophy and PAH. Additionally, there may be therapeutic potential via recombinant BNP or neutral endopeptidase inhibitors in RV dysfunction and PAH. D 2004 The Canadian Society of Clinical Chemists. All rights reserved. Keywords: Natriuretic peptide; Right ventricular dysfunction; Pulmonary arterial hypertension Introduction Electron microscopy studies revealed the presence of atrial natriuretic peptide (ANP) in atrial granules some 25 years before its isolation [1,2]. Subsequently, other peptides, namely, B-type or brain natriuretic peptide (BNP), C-type natriuretic peptide (CNP) [3], and dendroaspis natriuretic peptide (DNP) [4], have also been isolated and character- ized. In general, the natriuretic peptides exhibit a range of actions throughout the body from fluid and pressure control to local neuroendocrine actions. For the remainder of this review, we will focus on those natriuretic peptides of cardiac origin, ANP and BNP. Both are synthesized by cardiac myocytes, and their production is increased by factors that increase cardiac pressure and volume overload [5]. The physiology, diagnostic, and therapeutic potentials of ANP and BNP in the context of ischemic heart disease and congestive heart failure (CHF) are well known [6–8]. In contrast to studies focusing on conditions involving left ventricular (LV) dysfunction, there have been few studies investigating the roles of the natriuretic peptides with respect to right ventricular (RV) dysfunction. Isolating the causes and conditions of natriuretic peptide release in RV dysfunction is important. In CHF, the RV may be involved due to volume or pressure overload and hence may con- 0009-9120/$ - see front matter D 2004 The Canadian Society of Clinical Chemists. All rights reserved. doi:10.1016/j.clinbiochem.2004.06.002 Abbreviations: ACE, angiotensin-converting enzyme; ANP, atrial natriuretic peptide; BNP, brain or B-type natriuretic peptide; CHF, congestive heart failure; CI, confidence interval; COPD, chronic obstructive pulmonary disease; CV, coefficient of variation; GC, guanylyl cyclase; LV, left ventricle or left ventricular; mPAP, mean pulmonary arterial pressure; NPR, natriuretic peptide receptor; PPH, primary pulmonary hypertension; PVR, pulmonary vascular resistance; RIA, radioimmunoassay; RV, right ventricle; RVEDP, right ventricular end diastolic pressure; TPR, total pulmonary resistance. * Corresponding author. Department of Cardiology, Homerton Univer- sity Hospital, NHS Trust, E9 6SR, London, UK. Fax: +44-208-5107687. E-mail address: lokyap@lycos.com (L.B. Yap). Clinical Biochemistry 37 (2004) 847 – 856