Effects Of Chronic Intermittent Hypobaric Hypoxia On Renal Sympathetic Nerve Activity In Anesthetized Rats

Objective: In recent years, it was proved by a number of experimental researches that Chronic Intermittent Hypobaric Hypoxia (CIHH) adaptation confers a protective effect on hearts against ischemia/reperfusion or hypoxia/reoxygenation injury. Our previous studies showed that the rats treated with CIHH mimicking 5000 m altitude (6 h/day, 28 days) displayed the cardioprotection clearly, including reducing infarct size, promoting recovery of myocardial contraction after ischemia/ reperfusion or hypoxia/reoxygenation, and anti-arrhythmia. The proposed mechanism of cardioprotection include increasing in antioxidant capabilities of myocardium, increasing of capillary density and coronary blood flow in heart, and increasing expression of heat shock protein (HSP) 70. Recently, our studies showed that CIHH had no effect on the hemodynamics of rats in basic normoxia condition, but it protected heart against the damage of contraction and the falling of blood pressure induced by acute hypoxia significantly. The further studies indicated that CIHH facilitated carotid sinus baroreflex in anesthetic rats, suggesting that neuroregulation played a role in cardiac protection of CIHH. Cardiac autonomic nervous system plays a major role in normal cardiac function and stablilization of blood pressure through neuroregulation by cardiac sympathetic nerve and cardiac vagus nerve. In addition, cardiac autonomic nervous system is involved in the change of cardiac function in a lot of pathological state. As a compensate mechanism, vagus nerve activity is decreased, but sympathetic nerve activity is increased during acute hypoxia, resulting in an increase in cardiac output and blood pressure to ensure sufficent blood supply to important organs such heart and brain. On the other hand, overaction of sympathetic nerve system is harmful for homeostasis of body and cardiac function. For example, overactive sympathetic nerve activity could induce arrhythmia and sudden death in cardiopath. Up to now, it is not well defined that effects of neuroregulation, especially sympathetic nerve system, on the cardiac protection of CIHH. The purpose of present study is to investigate the effects of CIHH on renal sympathetic efferent nerve activity and to explore the underlying mechanism in anesthetic rats.Method: Male Sprague-Dawley (SD) rats were randomly divided into four groups: control group (CON), 14-day CIHH treating group (CIHH14), 28-day CIHH treating group (CIHH28) and 42-day CIHH treating group (CIHH42). The CIHH rats were exposed to simulated high-altitude hypoxia in a hypobaric chamber mimicking 5000 m altitude (O2: 11.1%) 6 h per day for 14 d, 28 d and 42 d, respectively. The activities of rats were regularity observed and the body weight was recorded each week. The CON animals lived in the same environment as the CIHH animals with free access to food and water, except that they breathed normal room air. Before and during acute hypoxia, blood pressure (BP), heart rate (HR) and renal sympathetic efferent nerve activity (RSNA) in anesthetic rats were recorded simultaneously by using a set of biological function's experiment system connecting with the computer. After section of bilateral buffer nerves, the BP, HR and RSNA were recorded once again. A baroreflex functional curves and gain curves were constructed according to the change of RSNA induced by the change of BP through drug administration.Results: 1 There was no difference in HR, BP and blood gas between CIHH and CON animals in basic condition. 2 During ventilation with acute hypoxia gas, BP in the anesthetized rats decreased, HR increased and RSNA increased; the arterial partial pressures of oxygen (PaO2), the venous partial pressures of oxygen (PvO2), arteriovenous oxygen pressures gradient (Pa-vO2), the arterial partial saturation of oxygen (SaO2), and the venous partial saturation of oxygen (SvO2) decreased, while the arteriovenous oxygen saturation gradient (Sa-vO2) increased. During acute hypoxia, decreasing of BP was slighted, but increasing of HR and RSNA was enhanced in CIHH rats compared with CON animals. 3 Removing the buffer nerves had no effect on basic BP, HR, and RSNA in rats, but augmented the hypoxic decreasing reaction of BP, attenuated the hypoxic increasing reaction of HR and inhibited RSNA in rats. Compared to CON animals, acute hypoxia response of BP, HR and RSNA was blunt in CIHH animals after buffer nerves removing. 4 Phenylephrine (PE)-induced depressor reflex of CIHH increased markedly, manifesting as the shifting of baroreflex functional curves to the left and downward, the shifting of gain curves to the left and upward, and the decreasing of the lower plateau (P2) and BP in the midpoint of the curve (BP50), but the increasing of gain (P3) and Maximum gain (Gmax). Sodium Nitroprusside (SNP)- induced pressor reflex of CIHH also increased markedly, manifesting as the shifting of baroreflex functional curves to the right and upward, the shifting of gain curves to the right and upward, as well as the increasing of the upper plateau of the curve (P1), P3, BP50 and Gmax.Conclusion: Acute hypoxia decreases BP, increases HR and RSNA, while CIHH diminishes acute hypoxic decreasing of BP, augments acute hypoxic increasing of HR and RSNA, which related with the peripheral baroreflex, the peripheral chemoreflex and the central nerve system.