Chronic intermittent hypobaric hypoxia decreases β-adrenoceptor activity in right ventricular papillary muscle

Abstract

. Chronic intermittent hypobaric hypoxia decreases ␤-adrenoceptor activity in right ventricular papillary muscle. Am J Physiol Heart Circ Physiol 298: H1267-H1272, 2010. First published January 22, 2010 doi:10.1152/ajpheart.00410.2009.-Chronic intermittent hypobaric hypoxia (CIHH) has an effective cardiac protection against ischemia-reperfusion injury. However, the underlying mechanisms are not fully known. It has been shown that blockade of ␤-adrenergic receptor exerts anti-arrhythmic action and improves cardiac remodeling in ischemic myocardium. Thus we determined the influence of CIHH on ␤-adrenergic receptor activity in right ventricular papillary muscle of rats. We found that the action potential duration in right ventricular papillary muscle was significantly longer in CIHH rats than in control rats. Activation of ␤-adrenergic receptor with DL-isoproterenol dose-dependently increased action potential duration and the contractility in right ventricular papillary muscle. In CIHH rats, the prolonged effect of DL-isoproterenol on action potential duration and the positive inotropic effect were significantly decreased compared with that in control rats. Furthermore, radioligand-binding experiments revealed that the density and affinity of ␤-adrenergic receptor in right ventricular myocardium was significantly lower in CIHH rats. In addition, Western blot analysis revealed that the membrane-bound G protein Gs␣ expression level in cardiac myocardium was significantly lower in CIHH rats than that in control rats. Collectively, these data suggest that CIHH suppresses ␤-adrenergic receptor action in right ventricular papillary muscle through decreasing receptor density and affinity, as well as membrane-bound Gs␣. This mechanism may be involved in the cardiac protective effect of CIHH. action potential; contraction; intermittent hypoxia; ␤-adrenergic receptor; G protein LONG-TERM HIGH-ALTITUDE HYPOXIA can protect the heart against ischemia/hypoxia injury, including anti-arrhythmia and reduction of infarct size during acute ischemia (10). Chronic intermittent hypobaric hypoxia (CIHH), similar to the concept of ischemic preconditioning, also has significant protective effect on the heart against ischemia-reperfusion injury (1,21,28). Previous studies have demonstrated that CIHH inhibits ischemia-and reperfusion-induced Ca 2ϩ overloading in cardiac myocyte, preserves contractility of myocardium, and prevents apoptosis of cardiomyocytes (7,22,24). Multiple mechanisms or pathways are involved in the cardioprotection of CIHH. These mechanisms include the induction of heat-shock protein 70 (5, 25), increases in coronary flow and myocardial capillary angiogenesis (26), activation of ATP-sensitive K ϩ channels, inhibition of mitochondrial permeability transition pores (27,28), and activation of protein kinase C (6). However, the mechanisms underlying the anti-arrhythmic effect of CIHH are not fully known.The sympathetic nervous system is critically involved in the regulation of cardiac function through ␤-adrenergic receptors ...

Acclimatization to chronic intermittent hypoxia in mine workers: a challenge to mountain medicine in Chile

“…Hypobaric CIH preserves myocardial contractility and prevents apoptosis of cardiomyocytes (Beguin et al, 2007, Zhu et al, 2006, Zhang et al, 2004, increases coronary fl ow and myocardial capillary angiogenesis, activates ATP-sensitive K + channels and inhibits mitochondrial permeability transition pores (Zhong et al, 2002. A rat model of CIH has also provided evidence that CIH attenuates β-adrenergic receptor activity by decreasing β-adrenergic receptor density and affi nity in the right ventricle, and these alterations in the β-adrenergic receptor may contribute to cardiac protection in CIH (Guan et al, 2010).…”

KATP channels and MPTP are involved in the cardioprotection bestowed by chronic intermittent hypobaric hypoxia in the developing rat

“…[P B (barometric pressure) = 404 mmHg; P o 2 (partial pressure of oxygen) = 84 mmHg] for 6 h/day for 28 days develop significant cardioprotection against I/R injury, promoting the recovery of cardiac systolic function from I/R, limiting cardiac infarction and reducing arrhythmia [5][6][7]. The proposed mechanisms include enhancement of myocardial antioxidant capacity, increase in myocardial capillary density and coronary blood flow, attenuation of beta-adrenergic receptor activity, increase in the expression of the heat shock protein 70 family, activation of protein kinase C, decrease of I/R-induced apoptosis, opening of ATP-dependent (sensitive) potassium channels (K ATP channel) in both the cell and mitochondrial membranes and inhibition of the opening of the mitochondrial permeability transition pore (MPTP) [8][9][10][11][12][13][14].…”

Chronic Intermittent Hypobaric Hypoxia Ameliorates Ischemia/Reperfusion-Induced Calcium Overload in Heart via Na+/Ca2+Exchanger in Developing Rats

“…This CIHH-induced cardiac protection persists longer than ischemic preconditioning [13,14] and is associated with less side effects on the body, such as polycythemia, right ventricular hypertrophy and pulmonary hypertension compared with long-term adaptation to high-altitude hypoxia [15,16,17]. In addition, CIHH increases the electrical stability of the cell membrane, preserves the contractility of the myocardium, and prevents apoptosis of cardiomyocytes [18,19,20,21]. …”

“…Multiple mechanisms and pathways may be involved in the cardio-protective effect of CIHH, such as induction of heat shock protein 70 expression, promotion of myocardial capillary proliferation, activation of an ATP-sensitive potassium channel, inhibition of mitochondrial permeability transition pore opening, and activation of protein kinase C (PKC) [18,19,20,21,22,23,24,25]. It has also been reported that CIHH may contribute to maintaining Ca 2+ homeostasis and contraction by regulating the activity of ryanodine receptors (RyRs), sarcoplasmic reticulum Ca 2+ -ATPase protein, and NCX during I/R in adult rats [26].…”