Atrionatriuretic Peptide Improves Left Ventricular Function After Myocardial Global Ischemia–Reperfusion in Hypoxic Hearts

Abstract

Atrionatriuretic peptide (ANP) is reported to be useful for attenuating myocardial ischemia-reperfusion injury and improving left ventricular function after reperfusion. However, ANP may be either ineffectual or harmful in cases where the myocardium has been chronically hypoxic since birth. This can be a result of the concomitant high levels of cyclic guanosine monophosphate (cGMP) produced within the myocardium. This study aimed to verify the validity of using ANP to improve left ventricular function after myocardial ischemia-reperfusion injury. For this purpose, a cyanotic congenital disease model that was developed using isolated rat hearts was used. Hearts were obtained from Sprague-Dawley rats that were housed from birth until 6 weeks of age either in a hypoxic environment with 13-14% FiO(2) (hypoxic group) or in ambient air (normoxic group). These hearts were subjected to 30min of normothermic global ischemia followed by 30min of reperfusion using the Langendorff technique. Left ventricular functional recovery in hearts administered ANP (0.1µM) into the reperfusion solution was compared with those hearts that were not administered ANP in both hypoxic (without ANP: n=6, with ANP: n=6, with ANP and HS-142-1[an antagonist of ANP]: n=6) and normoxic hearts (without ANP: n =6, with ANP: n=6). In the hypoxic hearts, ANP administration improved the percent recovery of the left ventricular developed pressure (76.3±9.2% without ANP vs. 86.9±6.7% with ANP), maximum first derivative of the left ventricular pressure (82.4±1.1% without ANP vs. 95.8±6.5% with ANP), and heart rate (85.6±4.7% without ANP vs. 96.1±5.2% with ANP) after reperfusion. The improvement and recovery of these cardiac functions were closely related to significantly increased levels of postischemic cGMP release after ANP administration. The effect of ANP was blocked by HS-142-1. The improvements observed in the hypoxic group were similar to those found in the normoxic group. ANP administration during reperfusion improved left ventricular function after myocardial acute global ischemia-reperfusion equally in both the chronically hypoxic and age-matched normoxic groups.

The Role of Natriuretic Peptides in the Regulation of Cardiac Tolerance to Ischemia/Reperfusion and Postinfarction Heart Remodeling

“…Similarly, in studies performed in isolated perfused rat hearts, BNP and ANP prevented cardiac reperfusion injury after coronary occlusion and improved left ventricular function after cardiac global ischemia-reperfusion when added to the perfusion solution (Table 1). 52,71,73,75 In concordance with the ex vivo studies, in vivo studies in rats subjected to coronary occlusion (30 min) and reperfusion (4 h) showed that infusion of BNP (0.03 mg/kg min, i.v. ), starting 15 min before reperfusion until the end of reperfusion, decreased the IS/AAR ratio by approximately 50%.…”

Salviae Miltiorrhizae Liguspyragine Hydrochloride and Glucose Injection Protects Against Myocardial Ischemia-Reperfusion Injury and Heart Failure

“…ANP and BNP are closely related to MIR, and ANP was shown to improve cardiac function by promoting the release of cGMP in isolated hypoxic reperfusion rat heart [39]. ANP/PKG signaling pathway can regulate the K ATP channel of ventricular cardiomyocytes [40].…”

Morphological features of atrial myocardium embryonic development and its changes caused by hypoxia effect

“…In addition, many effects, including hypoxia, stimulate secretion (Casserly et al, 2010). The stimulating effect of hypoxia on the release of ANP is proved (Fujii et al, 2011). It is also known that under the influence of hypoxia, transcription of the ANP increases by activation of HIFs (hypoxia inducible factors) (Patterson & Zhang, 2010).…”