Response to Does the Wall Stress Alone Stimulate the Natriuretic Peptide System?
The proposition that cardiomyocyte “stretch” is a key determinant of brain natriuretic peptide (BNP) release has been a widely accepted concept that has contributed to the broad use of plasma BNP measurement in the diagnosis and evaluation of heart failure. In our study,1 we showed that the R2 value for the association between the transcardiac BNP gradient and left ventricular end-systolic wall stress was ≈0.5, indicating that 50% of the variability of cardiac BNP release was explained by hemodynamic factors, leaving a significant input from other signals. As recently reviewed by us, a number of factors other than hemodynamics relevant to the heart failure patient, including renal function, hemoglobin, body mass index, age, and sex, have been found to be related to plasma BNP concentrations.2 However, it remains unknown whether these associations are mediated by changes in BNP release or changes in BNP elimination from the plasma.
Apart from heart failure, it is also evident that plasma BNP levels can be significantly elevated in other situations. Severe sepsis and septic shock, often in combination with acute lung injury or acute respiratory distress syndrome may be associated with a marked rise in the plasma BNP concentration, reaching levels observed in patients with heart failure. Interestingly, also, in septic patients, an association between BNP and C-reactive protein levels is also observed,3 suggesting that sepsis-induced myocardial injury may contribute to natriuretic peptide release; however, a contribution from impaired BNP elimination is also possible. As suggested in their correspondence, Arjamaa and Nikinmaa4 also point out that hypoxia may also be a stimulus for BNP release. Consistent with this hypothesis, previous work has shown that transient myocardial ischemia induced by coronary occlusion leads to an increase in the BNP concentration in the coronary sinus in humans in vivo.5 In the absence of ischemia, it has also been demonstrated that exposure to experimental hypoxia in humans may lead to a rise in plasma natriuretic peptides, although the mechanism remains unknown.6 However, the likely relevance of a hypoxia-driven mechanism for BNP release to many forms of cardiovascular disease, including heart failure, would appear to be very limited, given that this response is only seen with a severe degree of hypoxia.
Sources of Funding
D.M.K. is supported by a Program Grant from the National Health and Medical Research Council of Australia.
Maeder MT, Mariani JA, Kaye DM. Hemodynamic determinants of myocardial B-type natriuretic peptide release: relative contributions of systolic and diastolic wall stress. Hypertension. 2010; 56: 682–692.
Arjamaa O, Nikinmaa M. Does the wall stress alone stimulate the natriuretic peptide system? Hypertension. 2010; 56: e175.
Pascual-Figual DA, Antolinos MJ, Bayes-Cenis A, Casas T, Nicolas F, Valdes M. B-type natriuretic peptide release in the coronary effluent following acute transient ischemia in humans. Heart. 2007; 93: 1077–1080.