Effects of Atorvastatin, Rosuvastatin, and Pravastatin on Antiplatelet Activity of Clopidogrel in Patients with Acute Coronary Syndrome and Different CYP2C19 Genotypes / 中国药学杂志

OBJECTIVE: To investigate the effects of atorvastatin, rosuvastatin, and pravastatin on antiplatelet activity of clopidogrel in patients with acute coronary syndrome(ACS) and different CYP2C19 genotypes. METHODS: Between November 2017 and November 2018, a total of 300 patients admitted for ACS were enrolled in this study and randomly assigned to three groups. All patients received standard dual antiplatelet therapy. A, B, and C groups received atorvastatin calcium 20 mg•d-1, rosuvastatin calcium 20 mg•d-1, and pravastatin sodium 20 mg•d-1, respectively. The CYP2C19 genotype was detected by pyrosequencing. Thromboelastogram(TEG) was applied to detect the ADP-induced platelet inhibition rate 7 days after treatment. RESULTS: No significant difference was observed in baseline clinical characteristics between three groups. It was also no statistically significant difference in ADP inhibition rate and proportion of clopidogrel resistance between three groups(P>0.05). However, compared with rosuvastatin group and pravastatin group, the ADP inhibition rate was significantly reduced in atorvastatin group in poor metabolizers of CYP2C19. CONCLUSION: In intermediate metabolizers and extensive metabolizers of CYP2C19, there is no significant difference in the effects of atorvastatin, rosuvastatin, and pravastatin on antiplatelet activity of clopidogrel. Compared with rosuvastatin and pravastatin, atorvastatin significantly attenuates the antiplatelet function of clopidogrel in poor metabolizers of CYP2C19.

Genotypes of adenoviruses in infants and young children with diarrhea / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the prevalence of adenoviruses (AdV) and their genotypes in infants and young children with diarrhea.</p><p><b>METHODS</b>A total of 380 children with diarrhea aged less than 3 years were enrolled. The genomic DNA was extracted from stool and PCR was used to detect AdV. Clone sequencing and genotyping were performed for DNA in AdV-positive specimens.</p><p><b>RESULTS</b>AdV was detected in 24 out of 380 specimens, and the detection rate was 6.3% (24/380). A majority of children with positive AdV were aged 2-3 years. The viral sequence analysis of positive specimens showed that the detection rates of enteric AdV41 and non-enteric AdV were 4.2% (16/380) and 2.1% (8/380), respectively, and among the children with non-enteric AdV, there were 2 with AdV1, 2 with AdV2, 1 with AdV7, 2 with AdV12, and 1 with AdV31.</p><p><b>CONCLUSIONS</b>Diarrhea caused by AdV is commonly seen in children aged 2-3 years, and AdV41 is the major predominant strain.</p>

Electrophysiological effects of hydrogen sulfide on human atrial fibers / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>It has been reported that endogenous or exogenous hydrogen sulfide (H(2)S) exerts physiological effects in the vertebrate cardiovascular system. We have also demonstrated that H(2)S acts as an important regulator of electrophysiological properties in guinea pig papillary muscles and on pacemaker cells in sinoatrial nodes of rabbits. This study was to observe the electrophysiological effects of H(2)S on human atrial fibers.</p><p><b>METHODS</b>Human atrial samples were collected during cardiac surgery. Parameters of action potential in human atrial specialized fibers were recorded using a standard intracellular microelectrode technique.</p><p><b>RESULTS</b>NaHS (H(2)S donor) (50, 100 and 200 µmol/L) decreased the amplitude of action potential (APA), maximal rate of depolarization (V(max)), velocity of diastolic (phase 4) depolarization (VDD) and rate of pacemaker firing (RPF), and shortened the duration of 90% repolarization (APD(90)) in a concentration-dependent manner. ATP-sensitive K(+) (K(ATP)) channel blocker glibenclamide (Gli, 20 µmol/L) partially blocked the effects of NaHS (100 µmol/L) on human atrial fiber cells. The L-type Ca(2+) channel agonist Bay K8644 (0.5 µmol/L) also partially blocked the effects of NaHS (100 µmol/L). An inhibitor of cystathionine γ-lyase (CSE), DL-propargylglycine (PPG, 200 µmol/L), increased APA, V(max), VDD and RPF, and prolonged APD(90).</p><p><b>CONCLUSIONS</b>H(2)S exerts a negative chronotropic action and accelerates the repolarization of human atrial specialized fibers, possibly as a result of increases in potassium efflux through the opening of K(ATP) channels and a concomitant decrease in calcium influx. Endogenous H(2)S may be generated by CSE and act as an important regulator of electrophysiological properties in human atrial fibers.</p>

Influences of Panax notoginsenosid on spontaneous contraction of small intestine smooth muscle of rabbits in vitro / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To observe the influences of Panax notoginsenosid(a compound of Chinese Traditional Medicine) on the spontaneous contraction of small intestine smooth muscle of rabbits in vitro and explore the mechanism.</p><p><b>METHODS</b>The influences of Panax notoginsenosid on the spontaneous contraction of small intestine in intacted rabbits(male or female) after the isothermal perfuse of small intestine in vitro were observed. Bay K8644 and nitro-L-arginine methylester (L-NAME) were added to the normal Tyrode's solution respectively before Panax notoginsenosid. In the Ca2+ free Tyrode's solution, rynodine was added before Panax notoginsenosid. The mechanism of Panax notoginsenosid was studied.</p><p><b>RESULTS</b>Panax notoginsenosid reduced the amplitude of contraction of small intestine smooth muscle in rabbits in a does-depended manner. Bay K8644 and L-NAME could completely block the inhibition of Panax notoginsenosid on the contraction of small intestine smooth muscle. Panax notoginsenosid inhibited significantly the intracellular calcium-depended contraction induced by rynodine in the Ca2+ free Tyrode's solution.</p><p><b>CONCLUSION</b>Panax notoginsenosid inhibits significantly the contraction of small intestine smooth muscle of rabbits in vitro. The mechanism may be related to increase NO concentration in small intestine smooth muscle so that inhibit extracellular Ca2+ inflowing via cell membrane and intracellular Ca2+ releasing via sarcoplasmic reticulum.</p>

Ginkgolide B inhibits carotid sinus baroreflex in anesthetized male rats / 生理学报

The effects of ginkgolide B on the carotid sinus baroreflex (CSB) were studied in the perfused isolated carotid sinus of 30 anesthetized Sprague-Dawley male rats. The results were as follows. (1) By perfusing with ginkgolide B (0.1, 1, 10 μmol/L), the functional curve of the baroreflex was shifted to the right and upward. There was a marked decrease in peak slope (PS) and reflex decrease (RD) in mean arterial pressure (P<0.01), while the threshold pressure (TP), equilibrium pressure (EP) and saturation pressure (SP) were significantly increased (P<0.05, P<0.01). Among the functional parameters of CSB, the changes in PS, RD, TP, EP and SP were dose-dependent. (2) Pretreatment with Bay K8644 (500 nmol/L), an agonist of L-type calcium channel, completely eliminated the effects of ginkgolide B (1 μmol/L) on the CSB. (3) Pretreatment with tetraethylammonium (TEA, 1 mmol/L), an inhibitor of potassium channel, completely abolished the above effects of ginkgolide B (1 μmol/L) on the CSB. These results suggest that ginkgolide B inhibits the CSB in anesthetized rats, which is mediated by decreased calcium influx and increased potassium efflux in baroreceptor nerve endings.

Electrophysiological effects of hydrogen sulfide on pacemaker cells in sinoatrial nodes of rabbits / 生理学报

The cardiac electrophysiological effects of hydrogen sulfide (H(2)S) on pacemaker cells in sinoatrial (SA) nodes of rabbits were examined using intracellular microelectrode technique. The results obtained were as follows: (1) The velocity of diastolic (phase 4) depolarization (VDD) and rate of pacemaker firing (RPF) in normal pacemaker cells in SA nodes were decreased by NaHS (H(2)S donor) (50, 100, 200 μmol/L) in a concentration-dependent manner; (2) ATP-sensitive K(+) (K(ATP)) channel blocker glybenclamide (Gli, 20 μmol/L) blocked the effect of NaHS (100 μmol/L) on pacemaker cells; (3) Pretreatment with CsCl (2 mmol/L), a blocker of pacemaker current (I(f)), did not affect the effect of NaHS (100 μmol/L) on SA node pacemaker cells; (4) DL-propargylglycine (PPG, 200 μmol/L), an inhibitor of cystathionine γ-lyase (CSE), did not affect the parameters of action potentials in pacemaker cells in SA nodes. All these results suggest that H(2)S exerts a negative chronotropic action on pacemaker cells in SA nodes of rabbits. These effects are likely due to an increase in potassium efflux through opening K(ATP) channels; I(f)is unlikely to play a major role in these effects. In our study, there was no evidence for the generation of endogenous H(2)S by CSE in SA node pacemaker cells.

Resveratrol inhibits electrical activity of paraventricular nucleus neurons in rat hypothalamic slices / 生理学报

To study the role of resveratrol in the discharges of neurons in paraventricular nucleus (PVN) in hypothalamic slices, extracellular single-unit discharge recording technique was used. The effects of resveratrol were examined with glass microelectrodes in the rat PVN neurons at resting potential level. The results were as follows: (1) In response to the application of resveratrol (0.05, 0.5, 5.0 μmol/L, n=29) to the superfusate for 2 min, the spontaneous discharge rate (SDR) of neurons in 28/29 (96.6%) hypothalamic slices significantly decreased in a dose-dependent manner; (2) Pretreatment with L-glutamate (0.2 mmol/L) led to a marked increase in the SDR in all 8/8 (100%) slices in an epileptiform pattern. The increased discharges were suppressed by the application of resveratrol (5.0 mmol/L) in all 8 slices; (3) In 8 slices, perfusion of the selective L-type calcium channel agonist, Bay K8644 (0.1 μmol/L), induced a significant increase in the discharge rate in 8/8 (100%) slices. Resveratrol (5.0 μmol/L) significantly attenuated the increased SDR in all 8 slices; (4) Pretreatment with the nitric oxide synthase (NOS) inhibitor N(ω)-nitro-L-arginine methyl ester (L-NAME, 50 μmol/L) increased SDR in 7/8 (87.5%) slices, but did not affect the inhibitory effect of resveratrol (5.0 μmol/L). These results suggest that resveratrol inhibits the electrical activity of PVN neurons and exerts neuroprotective actions on central neurons. The inhibitory effect of resveratrol is possibly related to the blockade of L-type calcium channel, but not due to NO release.

Effects of ginkgolide B on neuronal discharges in paraventricular nucleus of rat hypothalamic slices / 神经科学通报·英文版

<p><b>OBJECTIVE</b>To study the central role of ginkgolide B (BN52021) in regulating cardiovascular function of nerve center by examining the effects of ginkgolide B on the electrical activity of rat paraventricular nucleus (PVN) neurons in hypothalamic slice preparation and to elucidate the mechanism involved.</p><p><b>METHODS</b>Extracellular single-unit discharge recording technique.</p><p><b>RESULTS</b>(1) In response to the application of ginkgolide B (0.1, 1, 10 micromol/L; n = 27) into the perfusate for 2 min, the spontaneous discharge rates (SDR) of 26 (26/27, 96.30%) neurons were significantly decreased in a dose-dependent manner. (2) Pretreatment with L-glutamate (L-Glu, 0.2 mmol/L) led to a marked increase in the SDR of all 8 (100%) neurons in an epileptiform pattern. The increased discharges were suppressed significantly after ginkgolide B (1 micromol/L) was applied into the perfusate for 2 min. (3) In 8 neurons, perfusion of the selective L-type calcium channel agonist, Bay K 8644 (0.1 micromol/L), induced a significant increase in the discharge rates of 8 (8/8, 100%) neurons, while ginkgolide B (1 micromol/L) applied into the perfusate, could inhibit the discharges of 8 (100%) neurons. (4) In 8 neurons, the broad potassium channels blocker, tetraethylammonium (TEA, 1 mmol/L) completely blocked the inhibitory effect of ginkgolide B (1 micromol/L).</p><p><b>CONCLUSION</b>These results suggest that ginkgolide B can inhibit the electrical activity of paraventricular neurons. The inhibitory effect may be related to the blockade of L-type voltage-activated calcium channel and potentially concerned with delayed rectifier potassium channel (K(DR)).</p>

Electrophysiological effects of hydrogen sulfide on guinea pig papillary muscles in vitro / 生理学报

The cardiac electrophysiological effects of hydrogen sulfide (H2S) were examined in guinea pig papillary muscles in vitro using intracellular microelectrode technique. The results obtained were as follows: (1) the duration of action potential (APD) in the normal papillary muscles was decreased by NaHS (H(2)S donor, 50, 100, 200 micromol/L) in a concentration-dependent manner; (2) in partially depolarized papillary muscles, 100 micromol/L NaHS not only reduced APD, but also decreased the amplitude of action potential (APA), overshoot (OS) and maximal velocity of depolarization at phase 0 (V(max)); (3) pretreatment with ATP-sensitive K(+) (K(ATP)) channel blocker glibenclamide (20 micromol/L) partially blocked the effects of NaHS (100 micromol/L); (4) pretreatment with L-type Ca(2+) channel agonist Bay K8644 (0.5 micromol/L) also partially blocked the effects of NaHS (100 micromol/L); (5) pretreatment with Ca(2+)-free Krebs-Henseleit solution containing glibenclamide (20 micromol/L) completely blocked the effects of NaHS (100 micromol/L); (6) APD in the normal papillary muscles was increased by DL-propargylglycine (PPG, an inhibitor of cystathionine gamma-lyase, 200 micromol/L). All these results suggest that the electrophysiological effects of H(2)S on papillary muscles in our study are due to an increase in potassium efflux through the opening of K(ATP) channels and a decrease in calcium influx. Endogenous H(2)S may act as an important regulator in electrophysiological characters in papillary muscles.

Effect of resveratrol on baroreceptor activity of carotid sinus in anesthetized male rats / 药学学报

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 micromol x 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 N(omega)-nitro-L-arginine methyl ester (L-NAME, 100 micromol x 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 x L(-1)) abolished the effect of resveratrol on CBA. A potent inhibitor of tyrosine phosphatase (sodium orthovanadate, 1 mmol x 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.

Hydrogen sulfide facilitates carotid sinus baroreceptor activity in anesthetized male rats / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>It has been reported that hydrogen sulfide (H(2)S) could relax vascular smooth muscle by direct activation of K(ATP) channels and hyperpolarization of the membrane potential. Recently, our study has shown that H(2)S facilitated carotid baroreflex. This study was conducted to investigate the effect of H(2)S on carotid baroreceptor activity (CBA).</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>H(2)S (derived from NaHS) 25, 50 and 100 micromol/L facilitated CBA, which shifted FCCB to the left and upward. There was a marked increase in peak slope (PS) and peak integral value of carotid sinus nerve charge (PIV) in a concentration-dependent manner. Pretreatment with glibenclamide (20 micromol/L), a K(ATP) channel blocker, the above effects of H(2)S on CBA were abolished. Pretreatment with Bay K8644 (an agonist of calcium channels, 500 nmol/L) eliminated the role of H(2)S on CBA. An inhibitor of cystathionine gamma-lyase (CSE), DL-propargylglycine (PPG, 200 micromol/L) inhibited CBA in male rats and shifted FCCB to the right and downward.</p><p><b>CONCLUSIONS</b>Our results suggest that exogenous H(2)S exerts a facilitatory role on isolated CBA through opening K(ATP) channels and further closing the calcium channels in vascular smooth muscle. Endogenous H(2)S may activate CBA in vivo.</p>

Urotensin II inhibits electrical activity of hippoCampal CA1 neurons by potentiating the GABA(A) receptor-mediated Cl(-) current / 神经科学通报·英文版

Objective To examine the effects of urotensin II (UII) on the discharges of neurons in CA1 area of hippocampal slices by using extracellular recording technique. Results (1) In response to the application of UII (0.3, 3.0, 30.0, 300.0 nmol/L, n =77) into the perfusate for 2 min, the spontaneous discharge rates (SDR) of 63/77 (81.8%) neurons were significantly decreased in a dose-dependent manner. (2) Pretreatment with bicuculline (BIC, 100 mu mol/L), a specific GABA(A) receptor antagonist, led to a marked increase in the SDR of 6/7 (85.71%) 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 mu mol/L) , a selective blocker of Cl(-) channel, led to an increase in the SDR of all 8/8 (100%) neurons. The increased discharges were not influenced by the UII (30.0 nmol/L) applied. (4) Application of nitric oxide synthase (NOS) inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME, 50 mu mol/L) into the perfusate for 2 min also significantly augmented the SDR of 14/16 (87.5%) neurons , then UII (30.0 nmol/L) applied into the perfusate reduced the increased the SDR of all 14/14 ( 100% ) neurons. Conclusion These results suggest that UII may decrease neuronal activity by potentiating GABA(A) receptor-mediated Cl(-) current in hippocampal CA1 neurons, and involved with the mediation of nitric oxide.

Effect of intracerebroventricular injection of adrenomedullin on catecholaminergic neurons and expression of c-fos in the rat brain nuclei involved in cardiovascular regulation / 中国应用生理学杂志

<p><b>AIM AND METHODS</b>Using double immunohistochemical method for Fos and tyrosine hydroxylase(TH) to examine the effects of intracerebroventricular (icv) administration of adrenomedullin (AM) on catecholaminergic neurons and the expression of c-fos gene in rat brain nuclei involved in cardiovascular regulation in order to define whether the effects of central administration of adrenomedullin (AM) were induced by activating the catecholaminergic neurons.</p><p><b>RESULTS</b>(1) Following icy administration of AM (3 nmol/kg), Fos-like immunoreactivity neurons were markedly increased in several brain areas of the rat, including the brainstem, the hypothalamus and the forebrain. (2) Following icy administration of AM (3 nmol/kg), double-labeled neurons for Fos and TH increased significantly in the area postrema (AP), the nucleus of the solitary tract (NTS), the nucleus paragigantocellularis lateralis (PGL) and the locus coeruleus (LC). (3) Pretreatment with calcitonin gene-related peptide receptor antagonism CGRP (8-37) (30 nmol/kg) significantly reduced the action of AM (3 nmol/kg) in the brain.</p><p><b>CONCLUSION</b>AM activates the nuclei involved in cardiovascular regulation in the forebrain, the hypothalamus and the brainstem, and that the central actions of AM are induced by activating the catecholaminergic neurons of brainstem nuclei involved in cardiovascular regulation. CGRP receptor can mediate the effects of AM in brain.</p>

Adrenomedullin reduces intracellular calcium concentration in cultured hippocampal neurons / 生理学报

The effects of adrenomedullin (ADM) on intracellular calcium concentration ([Ca(2+)](i)) were investigated in cultured hippocampal neurons. Changes in [Ca(2+)](i) were detected by laser scanning confocal microscopy using Fluo 3-AM as the calcium fluorescent probe. [Ca(2+)](i) was represented by relative fluorescent intensity. The results showed that: (1) ADM (0.01-1.0 micromol/L) decreased the resting [Ca(2+)](i) in a concentration-dependent manner. (2) Calcitonin gene-related peptide receptor antagonist CGRP(8-37) significantly inhibited the effects of ADM. (3) ADM significantly reduced the increase in [Ca(2+)](i) induced by high K(+). (4) ADM markedly inhibited the inositol 1,4,5-trisphosphate (IP(3))-induced increase in [Ca(2+)](i), while did not influence ryanodine-evoked increase in [Ca(2+)](i). These results suggest that ADM reduces [Ca(2+)](i) in cultured hippocampal neurons through suppressing Ca(2+) release from IP(3)-sensitive stores. Although ADM does not alter resting Ca(2+) influx, it significantly suppresses Ca(2+) influx activated by high K(+). These effects may be partly mediated by CGRP receptors. ADM in the CNS may act as a cytoprotective factor in ischemic/hypoxic conditions.

Effects of genistein on intracellular free-calcium concentration in guinea pig ventricular myocytes / 生理学报

The effects of genistein (GST) on intracellular calcium concentration ([Ca(2+)](i)) were investigated in guinea pig ventricular myocytes. [Ca(2+)](i) was detected by confocal microscopy and represented by relative fluorescent intensity (FI-F(0)) /FI(0), %). The results showed that GST (10-40 micromol/L) reduced [Ca(2+)](i) in normal Tyrode's solution, Ca(2+)-free Tyrode's solution and normal Tyrode's solution containing 3 mmol/L EGTA in a concentration-dependent manner. The effects of GST on [Ca(2+)](i) in normal Tyrode's solution were partially inhibited by pretreatment with sodium orthovanadate, a potent inhibitor of protein tyrosine phosphatase, or L-type Ca(2+) channel agonist Bay K8644. GST also markedly inhibited the ryanodine-induced [Ca(2+)](i) responses in Ca(2+)-free Tyrode's solution. When Ca(2+) waves were produced by increasing extracellular Ca(2+) concentration from 1 to 10 mmol/L, GST (40 micromol/L) could block the propagating waves of elevated [Ca(2+)](i), and reduce the velocity and duration of propagating waves. These results suggest that GST may reduce the [Ca(2+)](i) in isolated guinea pig ventricular myocytes. The inhibition of voltage-dependent Ca(2+) channel, tyrosine kinase inhibition, and alleviation of Ca(2+) release from SR are possibly involved in the GST effect.

Capsaicin facilitates carotid sinus baroreflex in anesthetized rats / 生理学报

The effects of capsaicin (CAP) on the carotid sinus baroreflex were studied in 30 anaesthetized rats with perfused isolated carotid sinus. The results are as follows. (1) By perfusing the isolated carotid sinus with CAP (1 micromol/L), the functional curve of the baroreflex was shifted to the left and downward, with a peak slope (PS) increasing from 0.34+/-0.01 to 0.42+/-0.01 (P<0.01), whereas the reflex decrease (RD) in mean arterial pressure was enhanced from 36.51+/-1.26 to 45.01+/-0.71 mmHg (P<0.01). Meanwhile, the threshold pressure, equilibrium pressure and saturation pressure were all significantly decreased from 70.43 +/-2.09 to 52.86 +/-2.80 mmHg (P<0.01), 95.5+/-1.71 to 87.00+/-1.58 mmHg (P<0.01) and 177.60+/-1.37 to 163.55+/-2.12 mmHg (P<0.01), respectively. Among the functional parameters of carotid baroreflex, the changes in PS and RD induced by capsaicin were dose-dependent. (2) By pretreatment with ruthenium red (RR, 100 micromol/L), an antagonist of vanilloid receptor subtype 1 (VR(1)), the above effects of CAP on carotid baroreflex were abolished. (3) The CAP-induced change in the baroreflex was also eliminated by pretreatment with glibenclamide (20 microm ol/L), a K(ATP) channel blocker. On the basis of the results, it is concluded that CAP facilitates the carotid baroreflex, an effect of which may be resulted from the opening of K(ATP) channels mediated by VR(1).

Effects of low-dose capsaicin on L-type calcium current in guinea pig ventricular myocytes / 生理学报

The purpose of this study was to examine the effects of low-dose capsaicin (CAP) on L-type calcium current (I(Ca-L) ) in guinea pig ventricular myocytes and the underlying mechanism. I(Ca-L) was examined in isolated single guinea pig ventricular myocytes by using whole-cell patch clamp technique. CAP (1-25 nmol/L) increased the voltage-dependently activated peak amplitude of I(Ca-L) and downshifted the current-voltage (I-V) curve. CAP (1, 10, 25 nmol/L) increased the peak amplitude of I(Ca-L) from -9.67+/-0.7 pA/pF to -10.21+/-0.8 pA/pF (P>0.05), to -11.37+/-0.8 pA/pF and to -12.84+/-0.9 pA/pF (P<0.05), respectively. CAP 25 nmol/L shifted the steady-state activation curve of I(Ca-L) to the left and changed half activation potential (V(0.5)) from (-20.76+/-2.0) mV to (-26.71+/-3.0) mV (P<0.05), indicating that low-dose CAP may modify the voltage-dependent activation of calcium channel. Low-dose of CAP did not affect the steady-state inactivation curve of I(Ca-L) or half-recovery time of Ca(2+) channel from inactivation. Ruthenium red (RR, 10 micromol/L), a vanilloid receptor (VR1) blocker, antagonized the effects of low-dose CAP. These results suggest that low-dose CAP increases I(Ca-L) mainly by shifting its steady-state activation curve to the left. Such effects may be mediated by VR1.

Electrophysiological effects of capsaicin on spontaneous activity of rabbit atrioventricular node cells / 生理学报

To study the electrophysiological effects of capsaicin on spontaneous activity of rabbit atrioventricular (AV) node cells, parameters of action potential in AV node were recorded using intracellular microelectrode technique. Capsaicin (1-30 micromol/L) not only decreased the amplitude of action potential, maximal rate of depolarization (V(max)), velocity of diastolic (phase 4) depolarization, and rate of pacemaker firing, but also prolonged the duration of 90% repolarization of action potential (APD(90)) in a concentration-dependent manner. Both application of L-type Ca(2+) channel agonist Bay K8644 (0.5 micromol/L) and elevation of calcium concentration (5 mmol/L) in superfusate antagonized the effects of capsaicin on pacemaker cells. Pretreatment with ruthenium red (10 micromol/L), a capsaicin receptor blocker, did not affect the effects of capsaicin on AV node cells. Capsaicin exerted an inhibitory action on spontaneous activity of AV node cells in rabbits. These effects were likely due to reduction in calcium influx, but were not mediated by VR1.

Intracerebroventricular administration of adrenomedullin increases the expression of c-fos and activates nitric oxide-producing neurons in rat cardiovascular related brain nuclei / 生理学报

To define the action sites of adrenomedullin (ADM) in the rat brain, and to examine whether neuronal NO may participate in the actions of ADM, the present study was undertaken to examine the effects of i.c.v. administration of ADM on the induction of Fos protein and on nitric oxide-producing neurons in rat brain nuclei involved in cardiovascular regulation, using double immunohistochemical method for Fos and neuronal nitric oxide synthase (nNOS). Following i.c.v. administration of ADM (1 nmol/kg, 3 nmol/kg), Fos-like immunoreactivity neurons were markedly increased in several brain areas of the rat, including the nucleus of the solitary tract (NTS), the area postrema, the locus coeruleus, the parabrachial nucleus and the nucleus paragigantocelluaris laterialis (PGL) in the brainstem, the paraventricular nucleus (PVN), the supraoptic nucleus (SON) and the ventromedial hypothalamic nucleus in the hypothalamus, as well as the central amygdaloid nucleus and the lateral habenular nucleus in the forebrain. Following i.c.v. injection of ADM (1 nmol/kg, 3 nmol/kg), the number of double-labeled neurons for Fos and nNOS was increased in the PVN and SON. Small numbers of double-labeled neurons were also found in the NTS and PGL following i.c.v. injection of ADM (3 nmol/kg), while i.c.v. injection of ADM (1 nmol/kg) did not change the number of double-labeled neurons in the NTS and PGL. Pretreatment with calcitonin gene-related peptide receptor antagonist CGRP(8-37) (30 nmol/kg) significantly reduced the action of ADM (3 nmol/kg) in the brain. These results suggest that centrally administered ADM may increase the expression of c-fos in the forebrain, the hypothalamus and the brainstem and activate nitric oxide-producing neurons in the PVN, SON, NTS and PGL. These effects may be partly mediated by CGRP receptors.

Effect of genistein on L-type calcium current in guinea pig ventricular myocytes / 生理学报

This paper was aimed to study the effect of genistein (GST) on L-type calcium current (I(Ca,L)) in isolated guinea pig ventricular myocytes using whole cell patch-clamp recording technique. The results are as follows. (1) GST (10, 50, 100 micromol/L) reduced the voltage-activated peak amplitude of I(Ca,L) in a concentration-dependent manner. Daidzein (100 micromol/L), a structural analogue of GST which has little or no inhibitory effect on tyrosine kinase, produced no effect over the same concentration range on I(Ca,L) (n=5, P>0.05). (2) GST up- shifted the current-voltage (I-V) curve, but the characteristics of I-V relationship were not significantly altered, and the maximal activation voltage of I(Ca,L) was not different from that of control. GST did not affect the activation kinetics of I(Ca,L). (3) GST markedly shifted the steady-state inactivation curve of I(Ca,L) to the left, and accelerated the voltage-dependent steady-state inactivation of I(Ca,L). V(0.5) value was -28.6 +/-0.6 mV in the control and -32.8 +/-1.1 mV in the presence of GST. The kappa values were 5.8 +/-0.5 mV and 6.5 +/-0.9 mV, respectively (n=6, P<0.05). (4) GST markedly shifted the curve of time-dependent recovery of I(Ca,L) from the steady-state inactivation to the right, and slowed down the recovery of I(Ca,L) from inactivation (n=7, P<0.01). (5) Sodium orthovanadate (1 mmol/L), a potent inhibitor of tyrosine phosphatase, significantly inhibited GST-induced inhibition (n=6, P<0.01). From the results obtained it is concluded that genistein inhibits I(Ca,L) and acts on the inactivated state of L-type calcium channel. This inhibitory effect of GST involves protein tyrosine kinase inhibition in guinea pig ventricular myocytes.