Effects Of Chronic Intermittent Hypobaric Hypoxia On Carotid Sinus Baroreflex In Developing Rats

Objective: Our previous study showed that after exposure of chronic intermittent hypobaric hypoxia(CIHH) mimicking 5000m altitude for 28 days, 6h/day, the adult rats displayed a cardiac protection obviously, including increase of antioxidation, prevention of ischemia/reperfusion arrhythmia, limiting the falling of cardiac contraction and the ultramicrostructure injury of myocardium induced by acute ischemia and hypoxia. Also it was observed that CIHH had no effect on systemic arterial blood pressure (SABP) under normal condition, but effectively prevented the decrease of SABP during acute hypoxia. Carotid sinus and aortic arch baroreflex plays the key role in buffering the fluctuation of blood pressure and keeping blood pressure homeostasis. Our further research found that CIHH facilitated carotid sinus baroreflex(CSB), which might be one of the neuroregulation mechanisms for anti-hypotension and cardioprotection during acute hypoxia or ischemia.There are many differences in cardiac structure and function between adult and developing animals. More recently, we found that the developing rats did not display a cardiac protection, but a cardiac damage after 28-days CIHH exposure mimicking 5000m altitude that effectively induced the cardiac protection in adult rats. The result suggested that same protocol or level of CIHH can produce totally different results in adult or developing rats. The effect of same protocol of CIHH on CSB in developing rat has not been elucidated. The purpose of present study was to investigate the effect of CIHH on CSB and the underlying mechanism in developing rat.Methods: Neonatal male Sprague-Dawley rats were randomly divided into four groups: 42-day CIHH treatment group (CIHH42), 56-day CIHH treatment group (CIHH56), 42-day control group (Con42) and 56-day control group (Con56). CIHH neonatal rats with the maternal rats were exposed to hypoxia mimicking 5000 m altitude (O2:11.1%) in a hypobaric chamber for 42 and 56 days, 6h per day, respectively. The control animals lived in the same environment as the CIHH animals with free access to food and water excepting hypoxia. Isolated carotid sinus perfusion technique was used to record the CSB in anaesthetized developing rats. The parameters used to evaluate the CNS include Peak slope (PS), Reflex decrease (RD), Threshold pressure (TP), Equilibrium pressure (EP) and Saturation pressure (SP).Results:1. CIHH inhibits CSB in developing rats.Compared with Con 42 and Con 56 rats, the functional curves of CSB in CIHH 42 and CIHH 56 rats shifted upward and rightward. PS in CIHH42 and CIHH56 rats were 0.35±0.01 and 0.35±0.02 mmHg, respectively,markedly decreased (P<0.01) compared with 0.43±0.01 and 0.42±0.03 mmHg in Con 42 and Con 56 rats. RD in CIHH42 and CIHH56 rats were 36.64±1.48 and 36.36±2.12 mmHg, respectively, obviously decreased (P<0.01) compared with 43.71±2.59 and 42.66±2.76 mmHg in Con 42 and Con 56 rat. TP were 72.64±3.04 and 71.64±3.60 mmHg in CIHH42 and CIHH56,respectively, markedly increased (P<0.01) compared with 62.97±1.68 and 63.72±1.61mmHg in Con 42 and Con 56 rats. EP were 94.50±1.56 and 93.99±1.60mmHg in CIHH42 and CIHH56 , respectively, markedly increased (P<0.05) compared with 92.24±1.65 and 92.36±1.08 mmHg in Con 42 and Con 56 rats. SP were 181.94±4.18 and 181.56±5.23 mmHg,respectively, markedly increased (P<0.01) compared with 173.64±2.60 and 173.30±1.86 in Con42 and Con56 rats.2. Bay K 8644 can canceled the inhibitory effects of CIHH on CSB in developing rats.Bay K 8644(500 nmol/L), an agonist of L-type calcium channel, had no effect on functional parameters of CSB in developing rats. Bay K 8644 shifted functional curve of CSB downward and leftward in CIHH42 and CIHH56 rats. PS and RD were increased, TP and SP were decreased.3. L-NAME (100μmol/L) had no effect on CSB action of CIHH in developing rats.L-NAME (100μmol/L), an inhibitor of NO synthesis, had no effect on functional parameters of CSB in CIHH and Con rats.Conclusion: Taken together, Chronic Intermittent hypobaric Hypoxia inhibits CSB in anesthetized developing rats through blocking of L-type calcium channels in carotid sinus baroreceptor. The effect of CIHH on CSB is not related with NO.