Hypoxia exposure and B‐type natriuretic peptide release from Langendorff heart of rats

Abstract

AimWe studied whether available oxygen without induced mechanical stretch regulates the release of the biologically active B‐type natriuretic peptide (BNP) from Langendorff heart.MethodsRat hearts were isolated and perfused with a physiological Krebs–Henseleit solution at a constant hydrostatic pressure in Langendorff set‐up. The basal O2 level of perfusate (24.4 ± 0.04 mg L−1) was gradually lowered to 3.0 ± 0.01 mg L−1 over 20 min using N2 gas (n = 7). BNP and O2 level were measured from coronary flow. During control perfusions (n = 5), the O2 concentration was kept at 26.6 ± 0.3 mg L−1.ResultsA low oxygen concentration in the perfusate was associated with a significant increase in BNP release (F = 40.4, P < 0.001). Heart rate decreased when the oxygen concentration in the perfusate reached 9.1 ± 0.02 mg L−1 and continued to fall in lower oxygen concentrations (F = 14.8, P < 0.001). There was also a significant but inverse correlation between BNP and oxygen in the coronary flow (R 2 = 0.27, P < 0.001).ConclusionIn the spontaneously beating Langendorff rat heart, a decreasing concentration of oxygen in the ingoing perfusion increased the secretion of BNP. The effect of oxygen was independent of mechanical stretch of the heart as it occurred even when the heart rate decreased but the pressure conditions remained constant. The difference in the oxygen capacitance of blood and Krebs–Henseleit solution appears to be a major factor affecting secretion of BNP, which is correlated with the oxygen tension of myocardial cells and affected both by the oxygen concentration and capacitance of solution perfusing the heart and by the coronary flow.

Mitochondrial-Derived Vesicles Protect Cardiomyocytes Against Hypoxic Damage

“…The aorta was swiftly cannulated with a 21-gage cannula and the heart was retroactively perfused with Tyrode Solution (137 mM NaCl, 5.4 mM KCl, 1.2 mM MgCl 2 , 10 mM HEPES, 10 mM glucose, 1.2 mM NaH 2 PO 4 , and 1.2 mM CaCl 2 ) aerated with a mixture of O 2 (95%) and CO 2 (5%) in order to maintain O 2 levels at 800 nmol/mL using a murine Langendorff perfusion apparatus. After a stabilization period of 20 min, the perfusion buffer was switched to the Tyrode Solutions containing various O 2 concentrations (normoxia: 800 nmol/mL; mild hypoxia: 550 nmol/mL; heavy hypoxia: 300 nmol/mL), which have been proven to induce various myocardial injuries in previous studies (Anttila et al, 2017) for an additional 40 min of perfusion. Then, the hearts were cut into small pieces and homogenized in cold isolation buffer (20 mM HEPES, 220 mM mannitol, 68 mM sucrose, 80 mM KCl, 0.5 mM EGTA, 2 mM magnesium acetate, supplemented with protease inhibitors, pH 7.4) for mitochondrial isolation which was done using a protocol adapted from a previous study (McLelland et al, 2016).…”

The Endocrine Function of the Heart: Physiology and Involvements of Natriuretic Peptides and Cyclic Nucleotide Phosphodiesterases in Heart Failure

“…Arjamaa suggests that the role of NPs in hypoxia conditions is probably not to counterbalance pressure changes in the circulation, but to regulate oxygen transport causing a contraction of blood volume (diuresis, natriuresis, vascular permeability) leading to hemoconcentration and increased oxygen transport capacity per unit volume of blood [78]. In addition, Anttila et al [79] showed in a Langendorff rat beating-heart device that the BNP level of the infusate increases when the oxygen pressure of the infused solution decreases. The effect of oxygen was independent of the degree of mechanical stretching of the myocardium, even after the heart rate decreased while the pressure conditions remained constant.…”

Brain natriuretic peptide and right heart dysfunction after heart transplantation

“…Arjamaa suggests that the role of the natriuretic peptide system in hypoxia conditions is perhaps not to counterbalance pressure changes in circulation, but to regulate oxygen transport, by causing volume contraction (diuresis, natriuresis, and plasma shift) leading to hemoconcentration and increasing oxygen‐carrying capacity per unit volume of blood . Furthermore, Anttila et al . have shown in a spontaneously beating Langendorff rat heart, that the BNP level of perfusate is increased when the oxygen tension of the inflowing buffer is decreased.…”