B-type natriuretic peptide limits infarct size in rat isolated hearts via K_ATPchannel opening

Abstract

B-type natriuretic peptide (BNP) has been reported to be released from the myocardium during ischemia. We hypothesized that BNP mediates cardioprotection during ischemia-reperfusion and examined whether exogenous BNP limits myocardial infarction and the potential role of ATP-sensitive potassium (K(ATP)) channel opening. Langendorff-perfused rat hearts underwent 35 min of left coronary artery occlusion and 120 min of reperfusion. The control infarct-to-risk ratio was 44.8 +/- 4.4% (means +/- SE). BNP perfused 10 min before ischemia limited infarct size in a concentration-dependent manner, with maximal protection observed at 10(-8) M (infarct-to-risk ratio: 20.1 +/- 5.2%, P < 0.01 vs. control), associated with a 2.5-fold elevation of myocardial cGMP above the control value. To examine the role of K(ATP) channel opening, glibenclamide (10(-6) M), 5-hydroxydecanoate (5-HD; 10(-4) M), or HMR-1098 (10(-5) M) was coperfused with BNP (10(-8) M). Protection afforded by BNP was abolished by glibenclamide or 5-HD but not by HMR-1098, suggesting the involvement of putative mitochondrial but not sarcolemmal K(ATP) channel opening. We conclude that natriuretic peptide/cGMP/K(ATP) channel signaling may constitute an important injury-limiting mechanism in myocardium.

Natriuretic Peptides as an Adjunctive Treatment for Acute Myocardial Infarction

“…[4][5][6] Thereafter, several trials were conducted to determine the benefi cial role of ANP/BNP infusion on AMI; however, the results were confl icting. In order to provide a more robust evaluation of the potential benefi ts of ANP/BNP infusion in AMI patients, we performed a systematic review and meta-analysis.…”

“…4,5) The process of adverse left ventricular remodeling may be initiated soon after AMI, in which the renin-angiotensin-aldosterone system (RAAS) and endothelin play important roles. ANP and BNP have extensive physiological effects including diuresis, natriureis, antifi brosis, antihypertrophy, anti-inflammation and inhibition of sympathetic nerve activity, RAAS, and endothelin synthesis.…”

“…3) Previous experimental studies revealed that natriuretic peptide infusion could limit myocardial infarct size and prevent reperfusion arrhythmia in myocardial ischemia-reperfusion injured rats. [4][5][6] Thereafter, several trials were conducted to determine the benefi cial role of ANP/BNP infusion on AMI; however, the results were confl icting. In order to provide a more robust evaluation of the potential benefi ts of ANP/BNP infusion in AMI patients, we performed a systematic review and meta-analysis.…”

Cardiomyocyte‐restricted over‐expression of C‐type natriuretic peptide prevents cardiac hypertrophy induced by myocardial infarction in mice

“…Pre-ischaemic infusion of ANP or BNP has been shown to elicit protective effects against I/R in isolated rat hearts [24,25]. However, the possible mechanisms for the cardioprotective effects of the three natriuretic peptides on I/R seem to be controversial.…”

“…NPRC activation is thought to be responsible for the cardioprotective role of CNP as mentioned above, and the selective agonist of NPRC (cANF [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23] ) also reduces infarct size and maintains coronary perfusion pressure [12]. Studies of ANP and BNP effects show the involvement of cGMP generated via the NPRA receptor in the reduction of infarct size [24,25]. Interestingly, increased cGMP supply in transgenic mice selectively over-expressing endothelial nitric oxide synthase (eNOS) in cardiomyocytes was also implicated in attenuating myocardial I/R injury in an ex vivo model [26].…”