Search

Ejaculation is mediated by a spinal generator, which integrates inputs related to the sexual activity and coordinates sympathetic, parasympathetic, and motor outflow. Previous clinical studies indicate that primary premature ejaculation is related to the hyperactivity of the sympathetic nervous system. In this study, we explored the roles of N-methyl-D-aspartic acid ( NMDA) receptors in paraventricular nucleus of the hypothalamus ( PVN) on ejaculatory responses and its potential mechanism in the rats. We found that microinjection of 0.20 nmol NMDA into the PVN reduced the latency of intromission and facilitated ejaculation during copulation. Moreover, delayed ejaculation and intromission were observed after the rats were microinjected with NMDA receptor antagonist D (−)-2-Amino-5-phosphonopentanoic acid ( AP-5). However, we discovered that microinjection of NMDA into PVN significantly increased baseline lumbar splanchnic nerve activity ( LSNA), and the NMDA dose was positively correlated with the increased LSNA ( r = 0.875, p = 0.04). Meanwhile, the plasma norepinephrine level in rats injected with NMDA was much higher than that in rats injected with saline (1453.4 ± 136.4 pg/mL vs. 492.3 ± 36.8 pg/mL, p < 0.01). Additionally, AP-5 reduced the baseline LSNA and abrogated the enhancing activity of NMDA in LSNA. Thus, we propose that NMDA receptors in PVN may facilitate ejaculation through enhancing the activity of sympathetic system. [ABSTRACT FROM AUTHOR]

Background Adipose afferent reflex ( AAR) contributes to sympathetic activation and hypertension. Paraventricular nucleus ( PVN) plays an important role in AAR and sympathetic outflow. The aim of the present study was to determine whether PVN mediates AAR response to insulin in a rat model of insulin resistance ( IR). Methods Male Sprague-Dawley rats were randomly divided into Control and IR groups. Insulin resistance was induced by supplementing fructose (125 g L−1, 12 weeks) in the drinking water. Renal sympathetic nerve activity ( RSNA) and mean arterial pressure ( MAP) were recorded in anesthetized rats. AAR was evaluated by the RSNA and MAP responses to injection of capsaicin into four sites of right inguinal white adipose tissue. Results Rats in IR group showed a rise in plasma noradrenaline ( NE), glucose, insulin and triglyceride levels, left ventricular weight, systolic blood pressure, homeostasis model assessment of insulin resistance ( HOMA- IR) and PVN glucose and insulin levels, melanocortin 4 type receptors ( MC4Rs) protein expression, but not MC3Rs and insulin receptors. Compared with Control group, AAR in IR group was significantly enhanced, which contributed to the elevation of NE level; and insulin microinjection into the PVN or the third ventricle significantly strengthened AAR, which was attenuated by pre-treatment with MC4Rs antagonist HS024 and anti-insulin affibody, respectively, but not insulin receptors antagonist S961. Conclusion The enhanced AAR participates in sympathetic activation in IR, which can be strengthened by PVN insulin. PVN MC4Rs mediate the AAR response to insulin in IR, but not MC3Rs and insulin receptors. [ABSTRACT FROM AUTHOR]

Aim Cardiac sympathetic afferent reflex ( CSAR) participates in sympathetic over-excitation. Superoxide anions and angiotensin II (Ang II) mechanisms are associated with sympathetic outflow and CSAR in the paraventricular nucleus ( PVN). This study was designed to investigate whether PVN superoxide anions mediate CSAR and Ang II-induced CSAR enhancement response in fructose-induced insulin resistance ( IR) rats. Methods CSAR was evaluated with the changes of renal sympathetic nerve activity ( RSNA) and mean arterial pressure ( MAP) responses to the epicardial application of capsaicin ( CAP) in anaesthetized rats. Results Compared with Control rats, IR rats showed that CSAR, PVN NAD(P)H oxidase activity, superoxide anions, malondialdehyde ( MDA), Ang II and AT1 receptor levels were significantly increased, whereas PVN superoxide dismutase ( SOD) and catalase ( CAT) activities were decreased. In Control and IR rats, PVN microinjection of superoxide anions scavengers tempol, tiron and PEG- SOD (an analogue of endogenous superoxide dismutase) or inhibition of PVN NAD(P)H oxidase with apocynin caused significant reduction of CSAR, respectively, but DETC (a superoxide dismutase inhibitor) strengthened the CSAR. PVN pre-treatment with tempol abolished, whereas DETC potentiated, Ang II-induced CSAR enhancement response. Moreover, PVN pre-treatment with tempol or losartan prevented superoxide anions increase caused by Ang II in IR rats. Conclusion PVN superoxide anions mediate CSAR and Ang II-induced CSAR response in IR rats. In IR state, increased NAD(P)H oxidase activity and decreased SOD and CAT activities in the PVN promote superoxide anions increase to involve in CSAR enhancement. Ang II may increase NAD(P)H oxidase activity via AT1 receptor to induce superoxide anion production. [ABSTRACT FROM AUTHOR]

Aims Apelin is a specific endogenous ligand of orphan G protein-coupled receptor APJ. This study was designed to determine the roles and mechanisms of apelin-13 and APJ in paraventricular nucleus ( PVN) in renal sympathetic nerve activity ( RSNA), arginine vasopressin ( AVP) release and mean arterial pressure ( MAP) in spontaneously hypertensive rats ( SHR). Method Acute experiment was carried out in 13-week-old male SHR and Wistar-Kyoto rats ( WKY) under anaesthesia. RSNA and MAP responses to the PVN microinjection were determined. Apelin and APJ expressions were examined with quantitative real-time PCR and Western blot. AVP and noradrenaline were determined with ELISA. Osmotic minipumps were used for chronic PVN infusion in conscious WKY. Results Apelin and APJ in the PVN were up-regulated in SHR. The PVN microinjection of apelin-13 increased, but APJ antagonist F13A decreased the RSNA, MAP, plasma noradrenaline and AVP levels in SHR. N-methyl-D-aspartate receptor (NMDAR) antagonist plus non-NMDAR antagonist abolished the apelin-13-induced sympathetic activation rather than AVP release. NMDAR antagonist or non-NMDAR antagonist alone attenuated the apelin-13-induced sympathetic activation. Chronic infusion of apelin-13 into the PVN in normotensive rats induced hypertension, increased plasma noradrenaline and AVP levels and promoted myocardial atrial natriuretic peptide and beta-myosin heavy chain mRNA expressions, two indicative markers of cardiac hypertrophy. Conclusion Apelin-13 and APJ in the PVN contribute to hypertension via sympathetic activation and AVP release in SHR. The sympatho-excitatory effect of apeline-13 is mediated by both NMDAR and non- NMDAR in the PVN. Persistent activation of APJ in the PVN induces hypertension. [ABSTRACT FROM AUTHOR]

Aims Salusin- β in paraventricular nucleus ( PVN) increases renal sympathetic nerve activity ( RSNA), mean arterial pressure ( MAP), heart rate ( HR) and arginine vasopressin ( AVP) release in hypertensive rats but not in normal rats. The present study was designed to investigate the downstream molecular mechanism of salusin- β in the PVN in hypertension. Method Renovascular hypertension was induced by two-kidney, one-clip (2K1C) in male SD rats. Acute experiments were carried out 4 weeks after 2K1C or sham operation under anaesthesia. Results MrgA1 mRNA expression and salusin- β level in the PVN as well as plasma salusin- β level were increased in 2K1C rats. Bilateral PVN microinjection of salusin- β increased the RSNA, MAP and HR in 2K1C rats, which were abolished by the pre-treatment with polyethylene glycol-superoxide dismutase (PEG-SOD), the superoxide anion scavenger tempol, the NAD(P)H oxidase inhibitor apocynin or the protein kinase C (PKC) inhibitor chelerythrine chloride (CLC), but not affected by the AT1 receptor antagonist losartan, the Mas receptor antagonist A-779, the NOS inhibitor L-NAME or the GABAA and GABAB receptor antagonists gabazine+CGP-35348. Salusin- β-induced increases in superoxide anion level and NAD(P)H oxidase activity in the PVN were abolished by the PVN pre-treatment with CLC. Salusin- β increased AVP levels in rostral ventrolateral medulla and plasma, which were prevented by the pre-treatment with PEG-SOD, apocynin or CLC in 2K1C rats. Salusin- β augmented the enhanced activity of PKC in the PVN in 2K1C rats. Conclusion Protein kinase C- NAD(P)H oxidase-superoxide anions pathway in the PVN is involved in salusin- β-induced sympathetic activation, pressor response and AVP release in renovascular hypertension. [ABSTRACT FROM AUTHOR]

Excessive sympathetic activity contributes to the pathogenesis of hypertension and the progression of the related organ damage. Adipose afferent reflex ( AAR) is a sympatho-excitatory reflex that the afferent activity from white adipose tissue ( WAT) increases sympathetic outflow and blood pressure. Hypothalamic paraventricular nucleus ( PVN or PVH) is one of the central sites in the control of the AAR, and ionotropic glutamate receptors in the nucleus mediate the AAR. The AAR is enhanced in obesity and obesity hypertension. Enhanced WAT afferent activity and AAR contribute to the excessive sympathetic activation and hypertension in obesity. Blockage of the AAR attenuates the excessive sympathetic activity and hypertension. Leptin may be one of sensors in the WAT for the AAR, and is involved in the enhanced AAR in obesity and hypertension. This review focuses on the neuroanatomical basis and physiological functions of the AAR, and the important role of the enhanced AAR in the pathogenesis of obesity hypertension. [ABSTRACT FROM AUTHOR]

Aim Chemical stimulation of white adipose tissue ( WAT) induces adipose afferent reflex ( AAR) and results in increases in renal sympathetic nerve activity ( RSNA) and mean arterial pressure ( MAP). The enhanced AAR contributes to sympathetic activation and hypertension in obesity rats. This study was designed to investigate whether N-methyl- D-aspartate receptors ( NMDAR) and non- NMDAR in paraventricular nucleus ( PVN) modulate AAR and sympathetic outflow. Methods Renal sympathetic nerve activity and MAP were recorded in anesthetized rats. AAR was evaluated by the RSNA and MAP responses to the injection of capsaicin into the four sites of right inguinal WAT (8.0 nmol for each site). Results Bilateral PVN microinjection of NMDAR antagonist AP5 or MK-801, or non- NMDAR antagonist CNQX attenuated AAR, RSNA and MAP. AP5 + CNQX caused greater effects than AP5 or CNQX alone and almost abolished AAR. NMDAR agonist NMDA or non- NMDAR agonist AMPA enhanced the AAR, and increased RSNA and MAP, which were prevented by AP5 or CNQX pre-treatment respectively. Casein kinase 2 inhibitor DRB, NR2 A antagonist NVP- AAM077 or NR2 B antagonist CP-101,606 attenuated AAR, RSNA and MAP. NVP- AAM077 + CP-101,606 caused greater effects than NVP- AAM077 or CP-101,606 alone. Bilateral baroreceptor denervation and vagotomy enhanced AAR, which was abolished by PVN pre-treatment with AP5 + CNQX. Furthermore, AP5 + CNQX abolished the AAR induced by leptin in i WAT. Conclusion Both NMDAR and non- NMDAR in the PVN mediate AAR and contribute to the tonic control of sympathetic outflow and blood pressure. CK2, NR2A and NR2 B subunits of NMDAR in the PVN are involved in the NMDAR-mediated tonic control of AAR, RSNA and MAP. [ABSTRACT FROM AUTHOR]

Excessive sympathetic activity has a crucial role in the initiation and progression of chronic structural alterations in the heart and vessels associated with hypertension. Angiotensin II type 1a receptors (AT1aR) in paraventricular nucleus (PVN) are involved in sympathetic overdrive and hypertension. The present study was designed to investigate the cardiovascular beneficial effects of the AT1aR gene silence in the PVN in hypertension. The PVN microinjection of recombinant adenoviral vectors expressing either artificial microRNA (amiRNA) targeting AT1a receptors (Ad-miR-AT1a) or control microRNA (Ad-miR-Con) were carried out in spontaneously hypertensive rats (SHR) and normotensive Wistar rats. The vectors were labels with green fluorescent protein (GFP). The successful amiRNA interference was confirmed by the AT1 receptors reduction and the GFP expression in the PVN. Significant depressor effects were observed from day 5 to day 20 after Ad-miR-AT1a treatment in SHR. Ad-miR-AT1a treatment decreased the ratio of left ventricular weight to body weight, cross-sectional areas of myocytes, myocardial fibrosis, media thickness, and the media/lumen ratio of the aorta and the mesenteric artery in SHR. The amiRNA interference reduced the basal sympathetic activity, cardiac sympathetic afferent reflex, plasma norepinephrine and plasma angiotensin II in SHR. These results indicate that amiRNA interference targeting AT1aR in the PVN decreases arterial blood pressure, blunts sympathetic activity and improves myocardial and vascular remodeling in SHR. [ABSTRACT FROM AUTHOR]

Aim: This study was to determine the roles of inflammatory cytokines in paraventricular nucleus (PVN) in modulating sympathetic activity, blood pressure and cardiac sympathetic afferent reflex (CSAR). Methods: Renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) were recorded in anaesthetized rats with bilateral sinoaortic denervation and vagotomy. The CSAR was evaluated by the RSNA response to epicardial application of bradykinin (BK). The levels of inflammatory cytokines were measured with ELISA. Results: The PVN microinjection of pro-inflammatory cytokines (PIC), tumour necrosis factor (TNF)-α or interleukin (IL)-1β, increased the baseline MAP and RSNA, and enhanced the CSAR. Anti-inflammatory cytokines (AIC), IL-4 or IL-13, in the PVN only increased the baseline MAP. In the rats pretreated with TNF-α or IL-1β but not in the rats pretreated with IL-4 or IL-13, sub-response dose of angiotensin II caused significant increases in the MAP and RSNA and enhancement in the CSAR. AT1 receptor antagonist losartan in the PVN attenuated the effects of angiotensin II, TNF-α and IL-1β, but not the effects of IL-4 and IL-13. Stimulation of cardiac sympathetic afferents with epicardial application of BK increased the levels of TNF-α, IL-1β but not IL-4 in the PVN. Conclusion: TNF-α or IL-1β in the PVN increases blood pressure and sympathetic outflow and enhances the CSAR, which is partially dependent on the AT1 receptors, while IL-4 or IL-13 in the PVN only increases blood pressure. There is a synergetic effect of Ang II with TNF-α or IL-1β on blood pressure, sympathetic activity and CSAR. [ABSTRACT FROM AUTHOR]

Aim: The aim of the present study was to investigate whether reactive oxygen species (ROS) in rostral ventrolateral medulla (RVLM) modulate cardiac sympathetic afferent reflex (CSAR) and the enhanced CSAR response caused by microinjection of angiotensin II (Ang II) into the paraventricular nucleus (PVN). Methods: Under urethane and α-chloralose anaesthesia, renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) were recorded in sinoaortic-denervated and cervical-vagotomized rats. The CSAR was evaluated by the RSNA response to epicardial application of capsaicin (1.0 nmol). Results: Bilateral RVLM microinjection of tempol (a superoxide anion scavenger) or polyethylene glycol-superoxide dismutase (PEG-SOD, an analogue of endogenous superoxide dismutase) attenuated the CSAR, but did not cause significant change in baseline RSNA and MAP. NAD(P)H oxidase inhibitors apocynin or phenylarsine oxide (PAO) also showed similar effects, but SOD inhibitor diethyldithio-carbamic acid (DETC) enhanced the CSAR and baseline RSNA, and increased the baseline MAP. Bilateral PVN microinjection of Ang II (0.3 nmol) enhanced the CSAR and increased RSNA and MAP, which was inhibited by the pre-treatment with RVLM administration of tempol, PEG-SOD, apocynin or PAO. The pre-treatment with DETC in the RVLM only showed a tendency in potentiating the CSAR response of Ang II in the PVN, but significantly potentiated the RSNA and MAP responses of Ang II. Conclusion: These results suggest that the NAD(P)H oxidase-derived ROS in the RVLM modulate the CSAR. The ROS in the RVLM is necessary for the enhanced CSAR response caused by Ang II in the PVN. [ABSTRACT FROM AUTHOR]