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Angiotensin Type 1 Receptors and Superoxide Anion Production in Hypothalamic Paraventricular Nucleus Contribute to Capsaicin-Induced Excitatory renal reflex and Sympathetic Activation

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Neuroscience Bulletin 2020年第5期36卷 463-474页

作者： Yun Qiu Fen Zheng Chao Ye Ai-Dong Chen Jue-Jin Wang Qi Chen Yue-Hua Li Yu-Ming Kang Guo-Qing Zhu Key Laboratory of Targeted Intervention of Cardiovascular Disease Collaborative Innovation Center of Translational Medicine for Cardiovascular Diseaseand Department of PhysiologyNanjing Medical UniversityNanjing 211166China Department of Pathophysiology Nanjing Medical UniversityNanjing 211166China Department of Physiology and Pathophysiology Cardiovascular Research CenterXi'an Jiaotong University School of MedicineXi'an 710061China

Chemical stimulation of the kidney increases sympathetic activity and blood pressure in rats.The hypothalamic paraventricular nucleus(PVN)is important in mediating the excitatory renal reflex(ERR).In this study,we examined the role of molecular signaling in the PVN in mediating the capsaicin-induced ERR and sympathetic activation.Bilateral PVN microinjections were performed in rats under anesthesia.The ERR was elicited by infusion of capsaicin into the cortico-medullary border of the right kidney.The reflex was evaluated as the capsaicin-induced changes in left renal sympathetic nerve activity and mean arterial pressure.Blockade of angiotensin type 1 receptors with losartan or inhibition of angiotensin-converting enzyme with captopril in the PVN abolished the capsaicin-induced ERR.renal infusion of capsaicin significantly increased NAD(P)H oxidase activity and superoxide anion production in the PVN,which were prevented by ipsilateral renal denervation or microinjection of losartan into the PVN.Furthermore,either scavenging of superoxide anions or inhibition of NAD(P)H oxidase in the PVN abolished the capsaicin-induced ERR.We conclude that the ERR induced by renal infusion of capsaicin is mediated by angiotensin type 1 receptor-related NAD(P)H oxidase activation and superoxide anion production within the PVN.

关键词： renal reflex Sympathetic activity Blood pressure Paraventricular nucleus Angiotensin Reactive oxygen species

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Chemical Stimulation of renal Tissue Induces Sympathetic Activation and a Pressor Response via the Paraventricular Nucleus in Rats

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Neuroscience Bulletin 2020年第2期36卷 143-152页

作者： Chao Ye Yun Qiu Feng Zhang Ai-Dong Chen Hong Zhou Jue-Jin Wang Qi Chen Yue-Hua Li Yu-Ming Kang Guo-Qing Zhu Key Laboratory of Targeted Intervention of Cardiovascular Disease Collaborative Innovation Center of Translational Medicine for Cardiovascular Diseaseand Department of PhysiologyNanjing Medical UniversityNanjing 211166China Department of Physiology Nanjing Medical UniversityNanjing 211166China Department of Physiology and Pathophysiology Cardiovascular Research CenterXi’an Jiaotong University School of MedicineXi’an 710061China

Sympathetic activation and the kidney play critical roles in hypertension and chronic heart failure.The role of the kidney in sympathetic activation is still not well known.In this study,we revealed an excitatory renal reflex(ERR)in rats induced by chemical stimulation of the kidney that regulated sympathetic activity and blood pressure.The ERR was induced by renal infusion of capsaicin,and evaluated by the changes in renal sympathetic outflow,blood pressure,and heart rate.renal infusion of capsaicin dose-dependently increased the contralateral renal sympathetic nerve activity,mean arterial pressure,and heart rate.Capsaicin in the corticomedullary border had greater effects than in the cortex or medulla.Intravenous infusion of capsaicin had no significant effects.The effects of renal infusion of capsaicin were abolished by ipsilateral renal denervation,but were not affected by bilateral sinoaortic denervation.renal infusion of capsaicin increased the ipsilateral renal afferent activity.The ERR was also induced by renal infusion of bradykinin,adenosine,and angiotensin II,but not by ATP.renal infusion of capsaicin increased c-Fos expression in the paraventricular nucleus(PVN)of hypothalamus.Lesion of neurons in the PVN with kainic acid abolished the capsaicin-induced ERR.These findings indicate that chemical stimulation of kidney causes an excitatory reflex,leading to sympathetic activation,pressor response,and accelerated heart rate.The PVN is an important central nucleus in the pathway of the ERR.

关键词： Sympathetic activity Blood pressure renal afferents renal reflex Paraventricular nucleus

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