Inhibition of Carotid Sinus Baroreflex in Neonatal Rats Exposed to Chronic Intermittent Hypobaric Hypoxia

10.4077/CJP.2014.BAD275

Peng Xu；Xue-Bin Cao；Lu Gao；Hui-Jie Ma；Yi Zhang

The Chinese Journal of Physiology

57卷6期（2014 / 12 / 31）

343 - 349

英文

Chronic intermittent hypobaric hypoxia (CIHH) facilitates carotid sinus baroreflex (CSB) in adult rats, but the effect of CIHH on CSB in young rats is not known. The purpose of present study was to investigate the effect of CIHH on CSB in the young rat treated with CIHH from neonatal age, and the role of nitric oxide (NO) and Ca^(2+) in the effect of CIHH. Neonatal male Sprague-Dawley rats were randomly divided into three groups: 42-day CIHH treatment group (CIHH42), 56-day CIHH treatment group (CIHH56), and an age-matched control group (control). CIHH neonatal rats with the maternal rats were exposed to a simulated high-altitude hypoxia in a hypobaric chamber mimicking 5,000-m altitude (O_2 at 11.1 %) for 42 or 56 days, 6 h per day, respectively. Isolated carotid sinus perfusion technique was used to test CSB of the rats. After 42-day and 56-day CIHH exposure, the CSB of the rats was inhibited significantly, manifesting as decrease of peak slope (PS) and reflex decrease (RD), and increase of threshold pressure (TP), equilibrium pressure (EP) and saturation pressure (SP). This inhibitory effect was canceled by L-type calcium channel activator Bay K 8644, but not by nitric oxide synthase (NOS) inhibitor N^G-nitro-L-arginine methyl ester (L-NAME). The data showed that CIHH inhibited CSB in anesthetized young rats through blocking L-type calcium channels in carotid sinus baroreceptor.

1. Gao, L.,Guan, Y.,Cui, F.,Liu, Y.X.,Zhou, Z.N.,Zhang, Y.(2012).Facilitation of chronic intermittent hypobaric hypoxia on carotid sinus baroreflex in anesthetized rats.Chinese J. Physiol.,55,62-70.
   連結：
2. Béguin, P.C.,Belaidi, E.,Godin-Ribuot, D.,Levy, P.,Ribuot, C.(2007).Intermittent hypoxia-induced delayed cardioprotection is mediated by PKC and triggered by p38 MAP kinase and Erk1/2.J. Mol. Cell. Cardiol.,42,343-351.
3. Béguin, P.C.,Joyeux-Faure, M.,Godin-Ribuot, D.,Levy, P.,Ribuot, C.(2005).Acute intermittent hypoxia improves rat myocardium tolerance to ischemia.J. Appl. Physiol.,99,1064-1069.
4. Behm, R.,Honig, A.,Griethe, M.,Schmidt, M.,Schneider, P.(1984).Sustained suppression of voluntary sodium intake of spontaneously hypertensive rats (SHR) in hypobaric hypoxia.Biomed. Biochem. Acta,43,975-985.
5. Chapleau, M.W.,Abboud, F.M.(1994).Modulation of baroreceptor activity by ionic and paracrine mechanisms: an overview.Braz. J. Med. Biol. Res.,27,1001-1015.
6. Chapleau, M.W.,Hajduczok, G.,Sharma, R.V.,Wachtel, R.E.,Cunningham, J.T.,Sullivan, M.J.,Abboud, F.M.(1995).Mechanisms of baroreceptor activation.Clin. Exp. Hypertens.,17,1-13.
7. Chen, L.,Lu, X.Y.,Li, J.,Fu, J.D.,Zhou, Z.N.,Yang, H.T.(2006).Intermittent hypoxia protects cardiomyocytes against ischemia-reperfusion injury-induced alterations in Ca2+ homeostasis and contraction via the sarcoplasmic reticulum and Na+/Ca2+ exchange mechanisms.Am. J. Physiol. Cell Physiol.,290,C1221-C1229.
8. Katiukhin, V.N.,Shliakhto, E.V.,Shuiskaia, G.A.(1979).Effect of discontinuous high- altitude barotherapy on the hemodynamics in arterial hypertension.Kardiologiia,19,107-108.
9. Liu, Y.X.,Dong, J.H.,Gao, L.,Ma, H.J.,Wu, Y.M.,Zhang, Y.,He, R.R.(2009).Inhibition of rhynchophylline on carotid sinus baroreceptor activity in anesthetized rats.Chinese J. Pharmacol. Toxicol.,23,161-167.
10. Ning, G.M.,Yang, X.L.,Li, H.Y.(2004).Modulation of baroreflex activity by exogenous and endogenous NO in SD rats.Spa. Medical & Biol. Engineering,17,391-396.
11. Pawar, A.,Peng, Y.J.,Jacono, F.J.,Prabhakar, N.R.(2008).Comparative analysis of neonatal and adult rat carotid body responses to chronic intermittent hypoxia.J. Appl. Physiol.,104,1287-1294.
12. Pires, P.R.L.,Santos, N.P.,Adona, P.R.,Natori, M.M.,Schwarz, K.R.L.,de Bem, T.H.C.,Leal, C.L.V.(2009).Endothelial and inducible nitric oxide synthases in oocytes of cattle.Anim. Reprod. Sci.,116,233-243.
13. Rodway, G.W.,Sethi, J.M.,Hoffman, L.A.,Conley, Y.P.,Choi, A.M.,Sereika, S.M.,Zullo, T.G.,Ryter, S.W.,Sanders, M.H.(2007).Hemodynamic and molecular response to intermittent hypoxia (IH) versus continuous hypoxia (CH) in normal humans.Transl. Res.,149,76-84.
14. Sharma, R.V.,Chaplcau, M.W.,Hajduczok, G.,Wachtel, R.E.,Waite, L.J.,Bhalla, R.C.,Abboud, F.M.(1995).Mechanical stimulation increases intracellular calcium in nodose sensory neurons.Neuroscience,66,433-441.
15. Trofimova, L.K.,Graf, A.V.,Maslova, M.V.,Dunaeva, T.Y.,Krushinskaia, Y.V.,Maklakova, A.S.,Baizhumanov, A.A.,Goncharenko, E.N.,Sokolova, N.A.(2008).Influence intermittent normobaric hypoxia during early organogenesis on the development of white rats.Izv. Akad. Nauk. Ser. Biol.,3,365-368.
16. Wang, C.Y.,Wu, Y.M.,Xiao, L.,Xue, H.M.,Wang, R.,Wang, F.W.,He, R.R.(2008).Ginkgolide B inhibits carotid sinus baroreflex in anesthetized male rats.Acta Physiol. Sin.,60,17-22.
17. Wang, Z.Z.,Bredt, D.S.,Fidone, S.J.,Stensaas, L.J.(1993).Neurons synthesizing nitric oxide innervate the mammalian carotid body.J. Comp. Neurol.,336,419-432.
18. Xiao, D.,Bird, I.M.,Magness, R.R.,Longo, L.D.,Zhang, L.(2001).Upregulation of eNOS in pregnant ovine uterine arteries by chronic hypoxia.Am. J. Physiol. Heart Circ. Physiol.,280,H812-H820.
19. Xu, W.Q.,Yu, Z.,Xie, Y.,Huang, G.Q.,Shu, X.H.,Zhu, Y.,Zhou, Z.N.,Yang, H.T.(2011).Therapeutic effect of intermittent hypobaric hypoxia on myocardial infarction in rats.Basic Res. Cardiol.,106,329-342.
20. Yi, X.L.,Fan. Z.Z.,He, R.R.(1993).An automatic system controlled by computer for carotid sinus perfusion.Chinese J. Apply. Physiol.,9,156-159.
21. Zhang, H.,Yang, C.Y.,Wang, Y.P.,Wang, X.,Cui, F.,Zhou, Z.N.,Zhang, Y.(2007).Effects of different modes of intermittent hypobaric hypoxia on ischemia/reperfusion injury in developing rat hearts.Acta Physiol. Sin.,59,660-666.
22. Zhang, Y.,Zhong, N.,Gia, J.,Zhou, Z.(2004).Effects of chronic intermittent hypoxia on the hemodynamics of systemic circulation in rats.Jpn. J. Physiol.,54,171-174.
23. Zhang, Y.,Zhong, N.,Zhu, H.F.,Zhou, Z.N.(2000).Antiarrhythmic and antioxidativc effects of intermittent hypoxia exposure on rat myocardium.Acta Physiol. Sin.,52,89-92.
24. Zhao, G.,He, R.R.(1991).The facilitating effect of atrial natriuretic peptide on the carotid sinus baroreflex function.Acta Physiol. Sin.,43,360-367.
25. Zhong, N.,Zhang, Y.,Zhu, H.F.,Wang, J.C.,Fang, Q.Z.,Zhou, Z.N.(2002).Myocardial capillary angiogenesis and coronary flow in ischemia tolerance rat by adaptation to intermittent high altitude hypoxia.Acta Pharmacol. Sin.,23,305-310.
26. Zoccal, D.B.,Bonagamba, L.G.H.,Oliveira, F.R.T.,Antunes-Rodrigues, J.,Machado, B.H.(2007).Increased sympathetic activity in rats submitted to chronic intermittent hypoxia.Exp. Physiol.,92,79-85.