BACKGROUND/AIMS: Chronic intermittent hypobaric hypoxia (CIHH) protects the heart against ischemia/reperfusion (I/R) injury. This study investigated the calcium homeostasis mechanism and the role of Na(+)/Ca(2+) exchanger (NCX) in the cardiac protective effect of CIHH in developing rats. METHODS: Neonatal male rats received CIHH treatment or no treatment (control) in a hypobaric chamber simulating 3000-meter altitude for 42 days. The left ventricular function of isolated hearts was evaluated after 30 minutes of ischemia and 60 minutes of reperfusion. Myocardial infarct size, intracellular Ca(2+) concentration ([Ca(2+)]i), Na(+)-Ca(2+) exchanger currents (I(Na/Ca)) in ventricular myocytes, and NCX1 protein level in the sarcolemmal membrane were determined. RESULTS: The recovery of cardiac function after I/R was improved, with the myocardial infarct size reduced, in CIHH rats compared with control rats (p<0.05). These effects were attenuated by Bay K8644, an L-type Ca(2+) channel agonist, or ryanodine, a sarcoplasmic reticulum Ca(2+) channel receptor activator. Furthermore, the increases in [Ca(2+)]i during I/R were blunted in CIHH rats, but this effect was abolished by Bay K8644 or chelerythrine, a protein kinase C (PKC) inhibitor. The I(Na/Ca) was decreased and the reversal potential of INa/Ca was shifted toward negative potential during simulated ischemia in the control cardiomyocytes (p<0.05). The inhibition of NCX1 protein expression during I/R was smaller in the CIHH rats than in the control rats (p<0.05). CONCLUSION: These data suggest that CIHH protects developing rat hearts during I/R by enhancing the resistance against calcium overload and by preserving normal I(Na/Ca) and NCX1 protein. PKC activation might be involved in this protective process of CIHH.
BACKGROUND/AIMS: Chronic intermittent hypobaric hypoxia (CIHH) protects the heart against ischemia/reperfusion (I/R) injury. This study investigated the calcium homeostasis mechanism and the role of Na(+)/Ca(2+) exchanger (NCX) in the cardiac protective effect of CIHH in developing rats. METHODS: Neonatal male rats received CIHH treatment or no treatment (control) in a hypobaric chamber simulating 3000-meter altitude for 42 days. The left ventricular function of isolated hearts was evaluated after 30 minutes of ischemia and 60 minutes of reperfusion. Myocardial infarct size, intracellular Ca(2+) concentration ([Ca(2+)]i), Na(+)-Ca(2+) exchanger currents (I(Na/Ca)) in ventricular myocytes, and NCX1 protein level in the sarcolemmal membrane were determined. RESULTS: The recovery of cardiac function after I/R was improved, with the myocardial infarct size reduced, in CIHHrats compared with control rats (p<0.05). These effects were attenuated by Bay K8644, an L-type Ca(2+) channel agonist, or ryanodine, a sarcoplasmic reticulum Ca(2+) channel receptor activator. Furthermore, the increases in [Ca(2+)]i during I/R were blunted in CIHHrats, but this effect was abolished by Bay K8644 or chelerythrine, a protein kinase C (PKC) inhibitor. The I(Na/Ca) was decreased and the reversal potential of INa/Ca was shifted toward negative potential during simulated ischemia in the control cardiomyocytes (p<0.05). The inhibition of NCX1 protein expression during I/R was smaller in the CIHHrats than in the control rats (p<0.05). CONCLUSION: These data suggest that CIHH protects developing rat hearts during I/R by enhancing the resistance against calcium overload and by preserving normal I(Na/Ca) and NCX1 protein. PKC activation might be involved in this protective process of CIHH.
Authors: Robert T Mallet; Eugenia B Manukhina; Steven Shea Ruelas; James L Caffrey; H Fred Downey Journal: Am J Physiol Heart Circ Physiol Date: 2018-04-13 Impact factor: 4.733
Authors: Emilio A Herrera; Jorge G Farías; Alejandro González-Candia; Stefania E Short; Catalina Carrasco-Pozo; Rodrigo L Castillo Journal: Mar Drugs Date: 2015-02-04 Impact factor: 5.118
Authors: Arkady Uryash; Jorge Bassuk; Paul Kurlansky; Francisco Altamirano; Jose R Lopez; Jose A Adams Journal: PLoS One Date: 2015-03-25 Impact factor: 3.240