Hypoxia stimulates release of ANP and BNP from perfused rat ventricular myocardium

Abstract

We determined the effect of hypoxia on cellular energy state and ventricular atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and endothelin-1 (ET-1) release in an isolated perfused heart preparation after removal of all atrial tissue in 21- to 24-mo-old Wistar-Kyoto rats. After a control period (14 min), the ventricles (n = 6) were exposed to 30 min of hypoxia by changing the gas mixture to N2-CO2 (95:5 vol/vol; hypoxic period) and back to O2-CO2 (95:5 vol/vol) for 30 min (reoxygenation period). Control hearts (n = 6) were perfused throughout the experiment (74 min) with oxygenated Krebs-Henseleit phosphate-free buffer. In parallel experiments, the metabolic state of oxygenated (n = 4) and hypoxic (n = 5) ventricles was assessed using 31P-nuclear magnetic resonance (31P-NMR). Hypoxia caused a rapid decrease in left ventricular peak systolic pressure associated with a 2.1-fold increase (27.6 +/- 2.2 to 58.0 +/- 13.1 fmol/ml; P < 0.05) in the concentration of immunoreactive (ir) ANP and a 1.6-fold increase (2.5 +/- 0.2 to 3.9 +/- 0.5 fmol/ml; P < 0.05) in the [irBNP] (where brackets signify concentration) in the perfusate. In contrast, perfusate [irET-1] (1.2 +/- 0.2 fmol/ml) did not change significantly during hypoxia. 31P-NMR showed that the [ATP]-to-[ADP].[Pi] ratio was reduced during hypoxia with a simultaneous increase in intracellular monophosphates and perfusate [irANP] and [irBNP]. The decrease in the cytosolic pH during hypoxia was small. High-performance liquid chromatography of the perfusates showed that the ANP-like immunoreactive material released corresponded to the processed, low-molecular weight peptide.(ABSTRACT TRUNCATED AT 250 WORDS)

Serum high-sensitivity C-reactive protein, amyloid-associated protein and N-terminal proBNP levels do not predict reversible myocardial ischaemia

“…In one study, increase in serum BNP levels during electrocardiographic exercise testing was found in patients with stable angina pectoris. Also, the rise in serum BNP levels was correlated with the size of the ischaemic myocardium, assessed with positron emission tomography 17. In patients with angiographically proven coronary artery disease, serum NT-proBNP levels were related to the extent and severity of coronary artery disease 18…”

Comparison of Positive Cases for B-type Natriuretic Peptide and ECG Testing for Identification of Precursor Forms of Heart Failure in an Elderly Population

“…Patients with unstable angina have been reported to exhibit elevated plasma BNP levels, 21,22) possibly due to ischemiainduced BNP production from the myocardium. 23) Although no subjects assigned to the coronary artery disease group in the present study showed clinically unstable angina, possible asymptomatic or subclinical myocardial ischemia due to exertion may increase myocardial BNP production and circulating levels. 8,23) Hence, a number of subjects with coronary artery disease were identified exclusively by BNP testing.…”

The Role of N terminal pro-BNP in assessing severity of Coronary Artery Disease: a prospective study

“…Thus a mechanism other than LV dysfunction might be responsible for the adverse outcome in patients with NSTEACS and high levels of NT-proBNP . Toth et al (25) have found evidence that tissue hypoxia alone triggers release of BNP in absence of LV dysfunction. These results were confirmed by a recent physiological study showing that ventricular BNP gene expression is up-regulated by myocardial hypoxia resulting in augmented plasma concentrations of BNP and NT-proBNP (26).…”