Effects of urotensin II (UII) on paraventricular nucleus (PVN) neurons of hypothalamus from brain slices of rats were examined by using extracellular recording technique. The results are as follows: (1) In response to application of UII (0.3, 3.0, 30.0, 300.0 nmol/L, n=39) into the perfusate for 2 min, the spontaneous discharge rates (SDR) of 32/39 (82.05% ) neurons were significantly decreased in a dose-dependent manner; (2) Pretreatment with bicuculline (BIC, 100 μmol/L), a specific GABAA receptor antagonist, led to a marked increase in SDR of 5/7 ( 71.43% ) neurons in an epileptiform pattern. The increased discharges were not significantly changed after UII ( 30.0 nmol/L ) was applied into the perfusate for 2 min; (3) Pretreatment with picrotoxin ( PIC, 50 μmol/L ), a selective blocker of Cl- channel, led to an increase in the SDR of all 12/12 (100%) neurons. The increased discharges were not influenced by the applied UII (30.0 nmol/L) for 2 min in 11/12 (91.67%) neurons; (4) Application of nitric oxide synthase (NOS) inhibitor NG-nitro-L-arginine methyl ester (L-NAME, 50 μmol/L ) into the perfusate could significantly augment the SDR of 11/12 ( 91.67% ) neurons , while UII ( 30.0 nmol/L ) applied into the perfusate for 2 min led the augmented SDR of all (12/12, 100%) neurons decrease. The results suggest that UII decreases the excitability of PVN neurons of hypothalamus by potentiating GABAA receptor-mediated Cl- current.

Objective To examine the effects of intracerebroventricular administration of adrenomedullin (AM) on the expression of Fos and spontaneous electric activity of area postrema (AP) neurons in sino-aortic denervated rats. Methods To determine the expression of Fos and the spontaneous electrical activity of AP neurons in male Sprague-Dawley rats by immunohistochemistry. Results Following Intracerebroventricular administration of AM (1 nmol/kg, 3 nmol/kg), Fos-like immunoreactive (Fos-LI) neurons and the discharge rate of AP neurons markedly increased. Pretreatment with calcitonin gene-related peptide(CGRP) receptor antagonist CGRP8-37 (30 nmol/kg) significantly inhibited the effects of AM (3 nmol/kg). Conclusion AM may activate the neurons in AP via CGRP receptors.

AIM To study the central role of genistein (GST) in regulating cardiovascular function of nervous center by examining the effects of GST on the electrical activity of rat paraventricular nucleus neurons in slice preparation and to elucidate the mechanism involved. METHODS Using extracellular single-unit discharge recording technique to examine discharges of neurons in paraventricular nucleus of hypothalamic slices at the resting potential level. RESULTS ①In response to the application of GST 10, 50 and 100 μmol·L-1, respectively, in the perfusate for 2 min, the spontaneous discharge rates (SDR) of neurons in 25/26 hypothalamic slices were significantly decreased in a concentration-dependent manner. ②Pretreatment with L-glutamate 0.2 mmol·L-1 led to a marked increase in the SDR of slices in an epileptiform pattern. GST 50 μmol·L-1 significantly attenuated the increased SDR in all 7 slices. ③In 8/8 slices, the G protein-coupled inwardly rectifying K+ channels (GIRKs) antagonist, tetraethylammonium 1 mmol·L-1 completely blocked the inhibitory effect of GST 50 μmol·L-1. ④Pretreatment with nitric oxide synthase inhibitor Nω-nitro-L-arginine methyl ester 50 μmol·L-1 increased SDR in all 7 slices, but did not affect the inhibitory effect of GST 50 μmol·L-1. CONCLUSION GST can inhibit the electrical activity of paraventricular neurons, and play a protective role on the central neurons. The inhibitory effect of GST may be related to the activation of GIRKs which induce K+ outward current and then engender the cell membrane hyperpolarization, but be not due to the NO release.

We examined the effects of intracerebroventricular ( i. c. v) administration of adrenomedullin (ADM) on catecholaminergic neurons and the expression of c-fos gene in rat brain nuclei involved in cardiovascular regulation using double immunohistochemical method for Fos and tyrosine hydroxylase (TH). The results showed that: ( 1 ) Following icy administration of ADM (3 nmol/kg) , double-labeled neurons for Fos and TH were significantly increased in the area postrema ( AP), the nucleus of the solitary tract ( NTS), the nucleus paragigantocelluaris laterialis (PGL) and the locus coeruleus (LC). (2) Pretreatment with calcitonin gene-related peptide receptor antagonis CGRP8-37 (30 nmol/kg) significantly reduced the action of ADM (3 nmol/kg) in the brain. The present study suggested that ADM might activate the neurons of the brain nuclei involved in cardiovascular regulation, and supported the hypothesis that the central action of ADM were induced by activating the catecholaminergic neurons of brainstem nuclei involved in cardiovascular regulation, CGRP receptor might mediate the effects of ADM.

AIM To study if cholecystokinin octapeptide (CCK-8) alter cardiovascular functions by its direct inhibitory effect on carotid sinus baroreceptor (CSB) activity. METHODS The functional curve of carotid baroreceptor (FCCB) was constructed and the functional parameters of carotid baroreceptor were measured by recording sinus nerve afferent discharge in anesthetized male rats with perfused isolated carotid sinus. RESULTS ① CCK-8 0.1, 0.5 and 1.0 μmol·L-1 shifted FCCB to the right and downward, with a marked decrease in peak slope and peak integral value of carotid sinus nerve discharge in a concentration-dependent manner, indicating the inhibitory effect of CCK-8 on CSB activity. ② Pretreatment with proglumide (100 μmol·L-1), a nonselective CCK receptor antagonist, or Bay K8644 (0.5 μmol·L-1), an agonist of calcium channel, partially attenuated the inhibitory effect of CCK-8 (0.5 μmol·L-1) on CSB activity. Pretreatment with L-NAME (100 μmol·L-1), an inhibitor of NO synthase, did not affect the inhibitory action of CCK-8. CONCLUSION CCK-8 inhibits CSB activity, which may be mediated by activating CCK receptors in the carotid sinus area and thereby resulting in an inhibition of stretch-sensitive channels and decrease in Ca2+ influx.

Objective To investigate the role of renal nerve in cardioprotection provided by renal ischemic preconditioning(RIP).Methods The effects of ischemia-reperfusion and RIP on the hemodynamics, myocardial oxygen consumption, epicardial electrography and infarct size were examined in anesthetized rabbit.Results During the 45 min of myocardial ischemia and 180 min of reperfusion, all hemodynamic parameters and myocardial oxygen consumption decreased progressively significantly. Epicardial electrographic ST-segment was elevated significantly during myocardial ischemia and return to baseline progressively in the course of reperfusion. The myocardial infarct size occupied 55.80±1.25% of area at risk,and RIP significantly reduced the myocardial infarct size to 36.51±2.80%(P＜0.01). The renal nerve section (RNS) per se didn't affect myocardial infarct size produced by ischemia-reperfusion, while cardioprotection afforded by RIP was completely abolished by RNS.Conlusion RIP have the protective effect on heart, and activation of renal afferents by transient ischemia-reperfusion play an important role in such a cardioprotection.

Extracellular single-unit discharge recording technique was used to examine the effects of Ginkgolide B (BN52021) on the discharges of neurons in CAI area of hippocampal slices and to elucidate the mechanisms involved.The results showed that:(1) In response to the application of ginkgolide B (0.1,1,10 βμmol/L; n =43) into the perfusate for 2 rain,the spontaneous discharge rates (SDR) of 42/43 (97.67%) neurons were significantly decreased in a dose-dependent manner; (2) Pretreatment with L-glutamate (L-Glu,0.2mmol/L) led to a marked increase in the SDR of all 10 (100%) neurons in an epileptiform pattern.The increased discharges were suppressed significantly after ginkgolide B (1 μmol/L) was applied into the perfusate for 2 rain; (3) In 8 neurons,perfusion of the selective L-type calcium channel agonist,Bay K 8644 (0.1 μmol/L),induced a significant increase in the discharge rate of 8/8 (100%) neurons.Ginkgolide B (1 μmoL/L) applied into the perfusate inhibited the discharges of 7/8 (87.5%) slices; (4) In 8 neurons,the broad potassium channels blocker,tetraethylammonium (TEA,1 mmol/L) completely blocked the inhibitory effect of ginkgolide B (1 μmol/L).These results suggest that ginkgolide B can inhibit the electrical activity of CAI neurons.The inhibitory effect may be related to the blockade of L-type voltage-activated calcium channel and may be concerned with delayed rectifier potassium channel (KDR),which indicated that ginkgolide B play a protective role on the central neurons.

AIM To elucidate the effect of rhynchophylline(Rhy) on carotid sinus baroreceptor activity (CBA). METHODS By recording sinus nerve afferent discharge activity with isolated carotid sinus perfusion, parameters of CBA, such as peak slope (PS), peak integral value (PIV), threshold pressure (TP) and saturation pressure (SP) were examined. ①Rhy 10, 50, and 100 μmol·L-1, dissolved in K-H solution, was perfused into isolated carotid sinus, then the effects of Rhy on parameters of CBA were observed while intrasinus pressure was altered in a stepwise manner. ②NG-nitro-L-arginine methyl ester (L-NAME) 10 mmol·L-1, tetraethylammonium (TEA) 1 mmol·L-1 and Bay K8644 500 nmol·L-1 were perfused into isolated carotid sinus, and effects of them on the response of carotid baroreceptor to Rhy were observed. RESULTS ① By perfusing the isolated carotid sinus with Rhy 10 μmol·L-1, PS decreased from (19.2±0.3)% to (18.2±0.1)%·kPa-1and the PIV decreased from (219.3±3.3)% to (199.1±3.8)%, while TP and SP increased from (8.2±0.3) to (9.1±0.1)kPa and (21.5±0.1) to (22.1±0.1)kPa, respectively. By perfusing with Rhy 50 and 100 μmol·L-1, the changes in PS, TP and SP were in concentration-dependent manner, and this indicated inhibitory effect of Rhy on CBA. ②Pretreatment with L-NAME 100 μmol·L-1 did not affect inhibitory action of Rhy 50 μmol·L-1 on CBA. ③Pretreatment with TEA 1 mmol·L-1 had no effect on inhibitory effect of Rhy 50 μmol·L-1 on CBA. ④Pretreatment with Bay K8644 500 nmol·L-1 could mostly attenuate effect of Rhy 50 μmol·L-1 on CBA. CONCLUSION Rhy inhibits CBA via blocking calcium influx in baroreceptor nerve ending.

This study is to evaluate the effect of resveratrol on carotid baroreceptor activity (CBA). The functional curve of carotid baroreceptor (FCCB) was constructed and the functional parameters of carotid baroreceptor were measured by recording sinus nerve afferent discharge in anesthetized male rats with perfused isolated carotid sinus. Resveratrol (30, 60 and 120 μmol·L-1) inhibited CBA, which shifted FCCB to the right and downward. There was a marked decrease in peak slope (PS) and peak integral value (PIV) of carotid sinus nerve charge in a concentration-dependent manner. Pretreatment with Nω-nitro-L-arginine methyl ester (L-NAME, 100 μmol·L-1), an inhibitor of nitric oxide synthase (NOS), eliminated the inhibitory effect of resveratrol. Pretreatment with Bay K8644 (an agonist of L-type calcium channel, 500 nmol·L-1) abolished the effect of resveratrol on CBA. A potent inhibitor of tyrosine phosphatase (sodium orthovanadate, 1 mmol·L-1) did not influence the effect of resveratrol on CBA. Resveratrol inhibits carotid baroreceptor activity, which may be mediated by the locally released NO and decreased calcium influx. Several studies have showed a cardioprotective effect of resveratrol, with the penetrating study of resveratrol, it may show a potential value in the clinical treatment of cardiovascular disease as an alternative medicine.

AIM To study the relationship between cardioprotective effects of resveratrol and carotid sinus baroreflex (CSB). METHODS The functional curve of the CSB was measured by recording changes in arterial pressure in anesthetized male rats with perfused isolated carotid sinus. RESULTS Resveratrol (30, 60 and 120 μmol·L-1) inhibited the CSB, which shifted the functional curve of the baroreflex to the right and upward. There were a marked decrease in peak slope and a reflex decrease of blood pressure, and also an increase in threshold pressure. Changes of these parameters showed a concentration-dependent manner. Pretreatment with Nω-nitro-L-arginine methylester (100 μmol·L-1), an inhibitor of nitric oxide synthase, and pretreatment with Bay K8644 (500 nmol·L-1), an agonist of L-type calcium channel, could both eliminate the inhibitory effect of resveratrol on CSB. A potent inhibitor of tyrosine phosphatase sodium orthovanadate (1 mmol·L-1) did not influence the effect of resveratrol on CSB. CONCLUSION Resveratrol inhibits carotid baroreflex, which may be mediated by the locally released NO and decreased calcium influx.