Superoxide Anions and NO in the Paraventricular Nucleus Modulate the Cardiac Sympathetic Afferent Reflex in Obese Rats

An enhanced cardiac sympathetic afferent reflex (CSAR) is involved in the sympathetic activation in renovascular hypertension. The present study was designed to determine the role of superoxide anions in the paraventricular nucleus (PVN) in mediating the enhanced CSAR and sympathetic activity in renovascular hypertension in the two-kidney, one-clip (2K1C) model. Sinoaortic denervation and vagotomy were carried out, and renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) were recorded under anesthesia. The CSAR was evaluated by the response of RSNA to the epicardial application of capsaicin. Superoxide anion levels and NAD(P)H oxidase activity in the PVN increased in 2K1C rats and were much higher in 2K1C rats than in sham-operated (sham) rats after the epicardial application of capsaicin or PVN microinjection of ANG II. In both 2K1C and sham rats, PVN microinjection of the superoxide anion scavenger tempol or the NAD(P)H oxidase inhibitor apocynin abolished the CSAR, whereas the SOD inhibitor diethyldithiocarbamic acid (DETC) potentiated the CSAR. Tempol and apocynin decreased but DETC increased baseline RSNA and MAP. ANG II in the PVN caused larger responses of the CSAR, baseline RSNA, and baseline MAP in 2K1C rats than in sham rats. The effects of ANG II were abolished by pretreatment with tempol or apocynin in both 2K1C and sham rats and augmented by DETC in the PVN in 2K1C rats. These results indicate that superoxide anions in the PVN mediate the CSAR and the effects of ANG II in the PVN. Increased superoxide anions in the PVN contribute to the enhanced CSAR and sympathetic activity in renovascular hypertension.

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Improved yield of obese rats using a double coordinate system to locate the ventromedial or paraventricular nucleus

Brain Research Bulletin ◽

10.1016/0361-9230(93)90074-l ◽

1993 ◽

Vol 32 (2) ◽

pp. 191-194 ◽

Cited By ~ 1

Author(s):

Katsuto Tokunaga ◽

George A. Bray ◽

Yuji Matsuzawa

Keyword(s):

Coordinate System ◽

Paraventricular Nucleus ◽

Obese Rats

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ANG II in the paraventricular nucleus potentiates the cardiac sympathetic afferent reflex in rats with heart failure

Journal of Applied Physiology ◽

10.1152/japplphysiol.00573.2004 ◽

2004 ◽

Vol 97 (5) ◽

pp. 1746-1754 ◽

Cited By ~ 67

Author(s):

Guo-Qing Zhu ◽

Lie Gao ◽

Kuashik P. Patel ◽

Irving H. Zucker ◽

Wei Wang

Keyword(s):

Heart Failure ◽

Electrical Stimulation ◽

Paraventricular Nucleus ◽

Sham Group ◽

Ang Ii ◽

Renal Sympathetic Nerve Activity ◽

Afferent Nerves ◽

Coronary Ligation ◽

Cardiac Sympathetic Afferent Reflex ◽

Renal Sympathetic

Chronic heart failure (CHF) is characterized by sympathoexcitation, and the cardiac sympathetic afferent reflex (CSAR) is a sympathoexcitatory reflex. Our previous studies have shown that the CSAR was enhanced in CHF. In addition, central angiotensin II (ANG II) is an important modulator of this reflex. This study was performed to determine whether the CSAR evoked by stimulation of cardiac sympathetic afferent nerves (CSAN) in rats with coronary ligation-induced CHF is enhanced by ANG II in the paraventricular nucleus (PVN). Under α-chloralose and urethane anesthesia, renal sympathetic nerve activity (RSNA) was recorded. The RSNA responses to electrical stimulation (5, 10, 20, and 30 Hz) of the CSAN were evaluated. Bilateral microinjection of the AT1-receptor antagonist losartan (50 nmol) into the PVN had no significant effects in the sham group, but it abolished the enhanced RSNA response to stimulation in the CHF group. Unilateral microinjection of three doses of ANG II (0.03, 0.3, and 3 nmol) into the PVN resulted in dose-related increases in the RSNA responses to stimulation. Although ANG II also potentiated the RSNA response to electrical stimulation in sham rats, the RSNA responses to stimulation after ANG II into the PVN in rats with CHF were much greater than in sham rats. The effects of ANG II were prevented by pretreatment with losartan into the PVN in CHF rats. These results suggest that the central gain of the CSAR is enhanced in rats with coronary ligation-induced CHF and that ANG II in the PVN augments the CSAR evoked by CSAN, which is mediated by the central angiotensin AT1 receptors in rats with CHF.

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Paraventricular nucleus is involved in the central pathway of cardiac sympathetic afferent reflex in rats

Experimental Physiology ◽

10.1113/expphysiol.2007.041632 ◽

2008 ◽

Vol 93 (6) ◽

pp. 746-753 ◽

Cited By ~ 54

Author(s):

Ming-Kui Zhong ◽

Yang-Can Duan ◽

Ai-Dong Chen ◽

Bo Xu ◽

Xing-Ya Gao ◽

...

Keyword(s):

Paraventricular Nucleus ◽

Cardiac Sympathetic Afferent Reflex

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Relative contributions of the thalamus and the paraventricular nucleus of the hypothalamus to the cardiac sympathetic afferent reflex

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00004.2013 ◽

2013 ◽

Vol 305 (1) ◽

pp. R50-R59 ◽

Cited By ~ 12

Author(s):

Bo Xu ◽

Hong Zheng ◽

Kaushik P. Patel

Keyword(s):

Arterial Pressure ◽

Paraventricular Nucleus ◽

Single Unit ◽

Thalamic Nucleus ◽

Control Group ◽

Unit Recording ◽

Hypothalamic Nuclei ◽

Mediodorsal Thalamic Nucleus ◽

Cardiac Sympathetic Afferent Reflex ◽

Intact Rats

The cardiac sympathetic afferent reflex (CSAR) is induced by stimulating the cardiac sympathetic afferents, which evokes increases in sympathetic outflow and arterial pressure. In the present study, we attempted to identify the contribution of thalamic and hypothalamic nuclei involved in the CSAR. First, we observed that there was an increase in the number of c-Fos-labeled cells in the paraventricular nucleus (PVN) (190 ± 18 vs. 101 ± 15; P < 0.05), the paraventricular nucleus of the thalamus (PVT) (239 ± 23 vs. 151 ± 15; P < 0.05), and the mediodorsal thalamic nucleus (MD) (92 ± 9 vs. 63 ± 6; P < 0.05) following epicardial application of bradykinin (BK) compared with the control group ( P < 0.05). Second, using extracellular single-unit recording, we found 25% of spontaneously active neurons in the thalamus were stimulated by epicardial application of BK or capsaicin in intact rats. However, 24% of spontaneously active neurons in the thalamus were still stimulated by epicardial application of BK or capsaicin despite vagotomy and sinoaortic denervation. None of the neurons in the thalamus responded to baroreflex changes in arterial pressure, induced by intravenous injection of phenylephrine or sodium nitroprusside. The CSAR was inhibited by microinjection of muscimol or lidocaine into the PVN. However, it was not inhibited or blocked by microinjection of muscimol or lidocaine into the thalamus. Taken together, these data suggest that the thalamus, while activated, is not critical for autonomic adjustments in response to activation of the CSAR. On the other hand, the PVN is critically involved in the central pathway of the CSAR.

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