Targeting at SUR2B/Kir6.1 subtype of ATP-sensitive potassium channel opener natakalim improves pressure overload-induced heart failure

Objective To explore the new stratigies targeting at SUR2B/Kir6.1 subtype against pressure overload-induced heart failure.Methods Pressure overload-induced heart failure was induced in Wistar rat by abdominal aortic banding(AAB).The effects of natakalim(1,3,9 mg·kg-1·d-1,10 weeks)were assessed on myocardial hypertrophy and heart failure,cardiac histology,vasoactive compounds,and gene expression.Isolated working heart and isolated tail artery helical strips were used to examine the influence of natakalim on heart and resistant vessels.Results Ten weeks after the onset of pressure overload,natakalim therapy potently inhibited cardiac hypertrophy and prevented heart failure.Natakalim inhibited the changes of left ventricular haemodynamic parameters,reversed the increase of heart mass index,left ventricular weight index and lung weight index remarkably.Histological examination demonstrated that there were no significant hypertrophy and fibrosis in hearts of pressure overload rat treated with natakalim.Ultrastructural examination of heart revealed well-organized myofibrils with mitochondria grouped along the periphery of longitudinally oriented fibers in natakalim group rats.The content of serum NO and plasma PGI2 was increased,while that of plasma ET-1 and cardiac tissue hydroxyproline,ANP and BNP mRNA was down-regulated in natakalim-treated rats.Natakalim at concentrations ranging from 0.01-100 μM had no effects on isolated working heart derived from Wistar rats;however,natakalim had endothelium-dependent vasodilation effects on the isolated tail artery helical strips precontracted with NE.Conclusions These results indicate that natakalim improves heart failure due to pressure overload by activating KATP channel SUR2B/Kir6.1 subtype and reversing endothelial dysfunction.     

The peroxisome proliferator-activated receptor-α （PPAR-α） agonist,AVE8134, attenuates the progression of heart failure and increases survival in rats

Aim： To investigate the efficacy of the peroxisome proliferator-activated receptor-α （PPARa） agonist, AVE8134, in cellular and experimental models of cardiac dysfunction and heart failure.
Methods： In Sprague Dawley rats with permanent ligation of the left coronary artery （post-MI）, AVE8134 was compared to the PPARy agonist rosiglitazone and in a second study to the ACE inhibitor ramipril. In DOCA-salt sensitive rats, efficacy of AVE8134 on cardiac hypertrophy and fibrosis was investigated. Finally, AVE8134 was administered to old spontaneously hypertensive rats （SHR） at a nonblood pressure lowering dose with survival as endpoint. In cellular models, we studied AVE8134 on hypertrophy in rat cardiomyocytes nitric oxide signaling in human endothelial cells （HUVEC） and LDL-uptake in human MonoMac-6 cells.
Results： In post-MI rats, AVE8134 dose-dependently improved cardiac output, myocardial contractility and relaxation and reduced lung and left ventricular weight and fibrosis. In contrast, rosiglitazone exacerbated cardiac dysfunction. Treatment at AVE8134 decreased plasma proBNP and arginine and increased plasma citrulline and urinary NOx/creatinine ratio. In DOCA rats, AVE8134 prevented development of high blood pressure, myocardial hypertrophy and cardiac fibrosis, and ameliorated endothelial dysfunction. Compound treatment increased cardiac protein expression and phosphorylation of eNOS. In old SHR, treatment with a low dose of AVE8134 improved cardiac and vascular function and increased life expectancy without lowering blood pressure. AVE8134 reduced phenylephrine-induced hypertrophy in adult rat cardiomyocytes. In HUVEC, Ser-1177-eNOS phosphorylation but not eNOS expression was increased. In monocytes, AVE8134 increased the expression of CD36 and the macrophage scavenger receptor 1, resulting in enhanced uptake of oxidized LDL.
Conclusion： The PPARa agonist AVE8134 prevents post-MI myocardial hypertrophy, fibrosis and cardiac dysfunction. AVE8134 has beneficial effects against hy     

Effects of imidapril on heterogeneity of action potential and calcium current of ventriclar myocytes in infarcted rabbits

AIM: To investigate the effects of chronic treatment with imidapril on the electrophysiologic heterogeneous change of the noninfarcted myocardium of rabbits after myocardial infarction and the mechanism of its antiarrhythmic efficacy. METHODS: Rabbits with left coronary artery ligation were prepared and allowed to recover for 8 weeks. Myocytes were isolated from subendocardial, midmyocardial, and subepicardial regions of the noninfarcted left ventricular wall. Action potentials and calcium current were recorded using whole-cell patch clamp technique. RESULTS: The action potential duration of repolarization 90% (APD90) was more prolonged in midmyocardium rather than in subepicardium and subendocardium with healed myocardial infarction. The transmural dispersion of repolarization (TDR) was increased in the three ventricular regions. The amplitude of ICa_L was enhanced but its density was decreased in noninfarcted ventricular myocytes due to increased cell membrane capacitance. The increased differences of     

Effects of AMP579 and adenosine on L-type Ca^2＋ current in isolated rat ventricular myocytes

Aim: To compare the effects of AMP579 and adenosine on L-type Ca^2 current (ICa-L) in rat ventricular myocytes and explore the mechanism by which AMP579 acts on ICa-L.Methods: ICa-L was recorded by patch-clamp technique in whole-cell configuration. Results: Adenosine (10nmol/L to 50μmol/L) showed no effect on basal ICa-L, but it inhibited the ICa-L induced by isoproterenol 10nmol/L in a concentration-dependent manner with the IC50 of 13.06μmol/L. Similar to adenosine,AMP579 also showed an inhibitory effect on the ICa-L induced by isoproterenol.AMP579 and adenosine (both in 10μmol/L) suppressed isoproterenol-induced ICa-L by 11.1% and 5.2%, respectively. In addition, AMP579 had a direct inhibitory effect on basal ICa-L in a concentration-dependent manner with IC50(1. 17μmol/L). PD116948 (30μmol/L), an adenosine A1 receptor blocker, showed no action on the inhibitory effect of AMP579 on basal ICa-L. However, GF109203X (0.4μmol/L), a special protein kinase C (PKC) blocker, could abolish the inhibitory effect of AMP579 on basal ICa-L. So the inhibitory effect of AMP579 on basal ICa-L was induced through activating PKC, but not linked to adenosine A1 receptor. Conclusion:AMP579 shows a stronger inhibitory effect than adenosine on the ICa-L induced by isoproterenol. AMP579 also has a strong inhibitory effect on basal ICa-L in rat ventricular myocytes. Activation of PKC is involved in the inhibitory effect of AMP579 on basal ICa-L at downstream-mechanism.     

Biphasic effects of haloperidol on sodium currents in guinea pig ventricular myocytes

Aim： To study the effects of haloperidol on sodium currents （INa） in guinea pig ventricular myocytes. Method： Whole-cell patch clamp technique was employed to evaluate the effects of haloperidol on INa in individual ventricular myocytes. Results： Haloperidol （0.1-3 wnol/L） inhibited INa in a concentration-dependent manner with an IC50 of 0.253±0.015 larnol/L. The inhibition rate of haloperidol （0.3 μmol/L） on INa was 22.14%±0.02%, and the maximum conductance was reduced. Haloperidol significantly reduced the midpoints for the activation and inactivation of INa by 2.09 and 4.09 mV, respectively. The time constant of recovery was increased. The increase in time intervals could only recover by 90.14%±1.4% （n=6）; however, haloperidol at 0.03 μmol/L enhanced INa conductance. The midpoints for the activation and inactivation Of INa were shifted by 1.38 and 5.69 mV, respectively, at this concentration of haloperidol. Conclusion： Haloperidol displayed a biphasic effect on INa in guinea pig cardiac myocytes. High concentrations of haloperidol inhibited INa, while lower concentrations of haloperidol shifted the activation and inactivation curve to the left. Full recovery of recovery curve was not achieved after 0.3 μmol/L haloperidol administration, indicating that the drug affects the inactivated state of sodium channels.     

Autologous transplantation of bone marrow mononuclear cells improved heart function after myocardial infarction

AIM: To investigate whether autologous transplantation of adult stem cells could improve post-infarcted heart function. METHODS: Bone marrow mononuclear cells (MNCs) were isolated from adult rabbits‘ tibias after coronary ligation. These cells were exposed to 5-azacytidine 10 μmol/L for 24 h on the third day of culture. After being labeled with bromodeoxyuridine (BrdU), the cells were auto-transplanted into bordering zone of the infarcted area at 2 weeks after injury. The animals were killed at 3 days, 2 weeks, 1 month, and 2 months after transplantation,respectively. The left ventricular functions, capillary density, and cardiac nerve density were measured and the differentiation of the engrafted cells was determined by immunostaining. RESULTS: BrdU-labeled MNCs were well aligned with the host cardiomyocytes. Parts of them were incorporated into capillary and arteriolar vessel wails. In addition to inducing angiogenic ligands (basic fibroblast growth factor, vascular endothelial growth factor) and imflammation cytokines (interleukin 1-β) during the early period of MNCs implantation, MNCs induced 2.0-fold increase in capillary density as well. Moreover, GAP43-positive and TH-positive nerve density were markedly higher in the MNCs-treated groups than that in the non-treated hearts. Left ventricular ejection fraction,LV dp/dtmax, and LV-dp/dtmax were 47 %, 67 %, and 55 % in MNCs-treated heart respectively, which was higher than that of the control heart, whereas left ventricular end-diastolic volume, left ventricular end-diastolic diameter,and left ventricular end-diastolic pressure were 45 %, 22 %, and 50 % respectively in MNCs-treated heart, which was lower than that of the control heart at 2 months after cell transplantation. CONCLUSION: Autologous transplantation of MNCs induced angiogenesis and nerve sprouting and improved left ventricular diastolic function.     

Effect of GW0742 on endothelial dysfunction induced by high glucose in isolated rat thoracic aorta北大核心CSCD

Aim To investigate the effect of GW0742 on the endothelial dysfunction induced by high glucose (glucose at 55 mmol · L-1) in isolated rat thoracic aorta and its related mechanisms. Methods The end othelium-dependent relaxation of acetylcholine was performed in the absence or presence of GW0742 at different concentrations under high glucose condition. The structure of aorta was observed by HE staining. Moreover , the content of NO was also measured by nitrate reduction method. The mRNA and protein expression were detected by quantitative real-time PCR and Western blot, respectively. Results Compared with the control group, acetylcholine-induced vasodilatation was impaired by high glucose. Meanwhile, the structures of endothelial cells and smooth muscle cells were also interrupted. Furthermore, the expressions of PPARβ mRNA and protein reduced while the NF-κB p65 expression increased significantly which occurred in parallei with decreasing eNOS expression and NO concentration (P <0. 01). GW0742 (0. 01, 0. 1, 1 μmol · L-1) restored the relaxation of acetylcholine in a dose-dependent manner, and reversed the mRNA and protein expression of PPARβ, NF-κB p65 and eNOS, as well as NO content (P < 0.01). Conclusion GW0742 attenuates the injury of endothelial dysfunction induced by high glucose, which may be, at least partly, mediated by the up-regulation of PPARβ, then the down-regulation of NF-κB, and the activation of eNOS-NO signal pathway.     

（—）Epicatechin induces and modulates endotheliumdependent relaxation in isolated rat mesenteric artery rings

AIM:The present study was aimed to examine the role of endothelial nitric oxide in the relaxant response to green tea (-)epicatechin and its modulation of endothelium-mediated relaxation in the isolated rat mesenteric artery rings.METHODS:Changes in the isometric tension were measured with Grass force-displacement transducers.RESULTS:The (-)epicatechin-induced relaxation was largely dependent on the presence of intact endothelium and was reversed by N^G-nitro-L-arginine methyl ester 10μmol/L or methylene blue 10μmol/L,the inhibitors of nitric oxidemediated relaxation.L-Arginine at 1mmol/L antagonized the effect of L-NAME or methylene blue.Pretreatment of endothelium-intact rings with (-)epicatechin 10μmol/L enhanced the relaxation induced by endothelium-dependent vasodilator,acetylcholine,while this concentration did not influence the endothelium-independent relaxation induced by sodium nitroprusside in the endothelium-denuded artery rings.CONCLUSION:The results indicate that the endothelium-dependent vasodilation by (-)epicatechin is mainly mediated through nitric oxide and low concentration of (-)epicatechin augments endothelium-dependent vasorelaxation in the rat mesenteric arteries.     

Puerarin blocks Na~+ current in rat ventricular myocytes

AIM: To study the effect of puerarin (Pue) on Na~+ channel in rat ventricular myocytes. METHODS: Whole-cell patch-clamp technique was applied on isolated cardiomyocytes from rats. RESULTS: Pue inhibited cardiac I_(Na) in a positive rate-dependent and dose-dependent manner, with an IC_(50) of 349 μmol/L. The kinetics of blockage of cardiac sodium channel by Pue resembled the ClassIa/Ic of antiarrhythmic agents. Pue 300 μmol/L did not alter the shape of the I-V curve of I_(Na), but markedly shifted the steady-state inactivation curve of I_(Na) towards more negative potential by 15.9 mV, and postponed the recovery of I_(Na) inactivation state from (21.9±1.6) ms to (54.4±3.4) ms (P<0.01 ). It demonstrated that the steady state of inactivation was affected by Pue significantly. CONCLUSION: Pue protected ventricular myocytes against cardiac damage and arrhythmias by inhibiting recovery from inactivation of cardiac Na~+ channels.     

Effects of docosahexaenoic acid on large-conductance Ca^2＋-activated K^＋ channels and voltage-dependent K^＋ channels in rat coronary artery smooth muscle cells

Aim： To investigate the effects of docosahexaenoic acid （DHA） on large-conductance Ca^2＋-activated K^＋ （BKca） channels and voltage-dependent K^＋ （Kv） channels in rat coronary artery smooth muscle cells （CASMCs）.
Methods： Rat CASMCs were isolated by an enzyme digestion method. BKCa and Kv currents in individual CASMCs were recorded by the patch-clamp technique in a whole-cell configuration at room temperature. Effects of DHA on BKCa and Kv channels were observed when it was applied at 10, 20, 30, 40, 50, 60, 70, and 80 μmol/L. Results： When DHA concentrations were greater than 10 μmol/L, BKCa currents increased in a dose-dependent manner. At a testing potential of ＋80 mV, 6.1%±0.3%, 76.5%±3.8%, 120.6%±5.5%, 248.0%±12.3%, 348.7%±17.3%, 374.2%±18.7%, 432.2%±21.6%, and 443.1%±22.1% of BKCr currents were increased at the above concentrations, respectively. The half-effective concentration （EC50） of DHA on BKca currents was 37.53±1.65 μmol/L. When DHA concentrations were greater than 20 μmol/L, Kv currents were gradually blocked by increasing concentrations of DHA. At a testing potential of ＋50 mV, 0.40%±0.02%, 1.37%±0.06%, 11.80%±0.59%, 26.50%±1.75%, 56.50%±2.89%, 73.30%±3.66%, 79.70%±3.94%, and 78.1%±3.91% of Kv currents were blocked at the different concentrations listed above, respectively. The EC50 of DHA on Kv currents was 44.20±0.63 μmol/L.
Conclusions： DHA can activate BKca channels and block Kv channels in rat CASMCs, and the EC50 of DHA for BKca channels is lower than that for Kv channels; these findings indicate that the vasorelaxation effects of DHA on vascular smooth muscle cells are mainly due to its activation of BKCa channels.     

Modulation of KATP currents in rat ventricular myocytes by hypoxia and a redox reaction

Aim： The present study investigated the possible regulatory mechanisms of redox agents and hypoxia on the KATP current （IKATP） in acutely isolated rat ventricular myocytes. Methods： Single-channel and whole-cell patch-clamp techniques were used to record the KATP current （IKATP） in acutely isolated rat ven- tricular myocytes. Results： Oxidized glutathione （GSSG, 1 mmol/L） increased the IKATP while reduced glutathione （GSH, 1 mmol/L） could reverse the increased IKATP during normoxia. To further corroborate the effect of the redox agent on the KATP channel, we employed the redox couple DTT （1 mmol/L）/H202 （0.3, 0.6, and 1 mmol/L） and repeated the previous processes, which produced results similar to the previous redox couple GSH/GSSG during normoxia. H202 increased the IKATP in a concentration dependent manner, which was reversed by DTr （1 mmol/L）. In addition, our results have shown that 15 min of hypoxia increased the IWTP, while GSH （1 mmol/L） could reverse the increased IKATP, Furthermore, in order to study the signaling pathways of the IKATP augmented by hypoxia and the redox agent, we applied a protein kinase C（PKC） inhibitor bisindolylmaleimide Vl （BIM）, a protein kinase G（PKG） inhibitor KT5823, a protein kinase A （PKA） inhibitor H-89, and Ca（2＋）/calmodulin-dependent protein kinase II （CaMKII） inhibitors KN-62 and KN-93. The results indicated that BIM, KT5823, KN-62, and KN-93, but not H-89, inhibited the IKATP augmented by hypoxia and GSSG; in addition, these results sug- gest that the effects of both GSSG and hypoxia on KATp channels involve the activation of the PKC, PKG, and CaMK II pathways, but not the PKA pathway. Conclusion： The present study provides electrophysiological evidence that hypoxia and the oxidizing reaction are closely related to the modulation of IKATP.     

Protective effects of betaglucin on myocardial tissue during myocardial infarction in rats and dogs

Aim： To test the protective effects of betaglucin, a novel beta-glucan, on models of myocardial infarction （MI） in rats and dogs. Methods： The left anterior descending （LAD） coronary artery occlusion model was used to induce an MI in rats and dogs. Three doses of betaglucin （10, 30 and 100 mg/kg）, propranolol （positive control, 1 mg/kg） and vehicle alone （5% glucose solution） were administered before LAD occlusion, and characteristics of the resulting MI were subsequently assessed. In anesthetized dogs, blood pressure heart rate, ventricular function, coronary artery blood flow and myocardial oxygen consumption were determined before and after the drug administration. Results： The MI mass in both rats and dogs was significantly reduced by betaglucin （30 and 100 mg/kg, P〈O.01） and propranolol （P〈O.01）. In anesthetized dogs, coronary artery blood flow was increased significantly by betaglucin （30 and 100 mg/kg, P〈O.01）, but blood pressure, heart rate and ventricular function were not changed （P〉O.05）. High-dose betaglucin （100 mg/kg） increased myocardial oxygen consumption, but not to a statistically significant level （P〉O.05）. The hemodynamic indexes were significantly changed by propranolol. Conclusion： Betaglucin has protective effects on myocardial tissue during MI in rats and dogs and has no influence on hemodynamic parameters at a therapeutic dose. The increase in coronary artery blood flow induced by betaglucin might be beneficial in the treatment of patients with MI.     

Supppressive effect of the immuno-suppressive protein induced by stress on arterrial blood pressure rat

To study the effect of partially purified immune suppressive protein of stress on the normal arterial blood pressure in rots.The immune suppressive protein of stress was partially purified from the lymph node of the restraint stressed rat with salting-out, extra-filtration and HPLC gel filtration.The protein was intravenously injected into normal SD rats.Blood pressure, heart rate and respiration were recorded with MacLab system.It was found that intravenous injection of the protein (200, 400, and 800 μg per     

去窦弓神经大鼠肥厚心室和主动脉的血管紧张素Ⅱ和AT1受体水平

AIM: Angiotensin II and AT1 receptor are the major effector components of renin-angiotensin system (RAS), andalso the main growth-stimulating factors in cardiovascular system. The present study was to observe these twofactors in the hypertrophied ventricles and aortas of sinoaortic-denervated rats. METHODS: Rats were examinedat 2, 10, and 16 weeks after sinoaortic denervation (SAD). The hypertrophy was evaluated by the ratio of organweight to body weight. Angiotensin II concentration and AT1 receptor mRNA expression were measured byradioimmunoassay and RT-PCR respectively, using a positive control of candesartan treatment. RESULTS: Aortichypertrophy existed in 2-, 10-, and 16-week SAD rats, left ventricular hypertrophy in 10- and 16-week SAD rats,and right ventricular hypertrophy in 16-week SAD rats. In all three kinds of examined SAD rats, plasma angiotensinII levels remained unchanged, indicating circulating RAS is at normal level in the chronic phase of SAD. However,cardiovascular tissue RAS was activated, as evidenced by increase of aortic angiotensin II concentrations at 10 and16 weeks after SAD, and up-regulation of aortic and left ventricular AT1 receptor mRNA expressions at 16 weeksafter SAD. CONCLUSION: The activated tissue RAS is secondary to the hypertrophy, and probably involved inthe maintenance of cardiovascular hypertrophy following SAD.     

Blockade of L-type calcium channel in myocardium and calcium-induced contractions of vascular smooth muscle by CPU 86017

AIM: To assess the blockade by CPU 86017 on the L-type calcium channels in the myocardium and on the Ca^2 -related contractions of vascular smooth muscle. METHODS: The whole-cell patch-clamp was applied to investigate the blocking effect of CPU 86017 on the L-type calcium current in isolated guinea pig myocytes and contractions by KCl or phenylephrine (Phe) of the isolated rat tail arteries were measured. RESULTS: Suppression of the L-type current of the isolated myocytes by CPU 86017 was moderate, in time- and concentration-dependent manner and with no influence on the activation and inactivation curves. The IC50 was 11.5 μmol/L. Suppressive effect of CPU 86017 on vaso-contractions induced by KCl 100 mmol/L, phenylephrine 1 μmol/Lin KH solution (phase 1),Ca^2 free KH solution ( phase 2), and by addition of CaCl2 into Ca^2 -free KH solution (phase 3) were observed. The IC50 to suppress vaso-contractions by calcium entry via the receptor operated channel (ROC) and Voltage-dependent channel (VDC) was 0.324μmol/L and 16.3μmol/L, respectively. The relative potency of CPU 86017 to suppress vascular tone by Ca^2 entry through ROC and VDC is 1/187 of prazosin and 1/37 of verapamil, respectively.CONCLUSION: The blocking effects of CPU 86017 on the L-type calcium channel of myocardium and vessel are moderate and non-selective. CPU 86017 is approximately 50 times more potent in inhibiting ROC than VDC.     

β阻滞剂阿替洛尔对绵羊急性心肌缺血后心室复极化离散度的影响

AIM: To investigate the effect of β-blockers on spatial dispersion of ventricular repolarization following acute myocardial ischemia. METHODS: Twenty sheep were randomized into control (normal saline, iv) and atenolol (1.5 mg/kg, iv) group. Acute myocardial ischemia was induced by occlusion of the obtuse marginal coronary artery. Unipolar ECG was simultaneously acquired from 64 epicardial sites in both ischemic and non-ischemic regions. Activation-recovery intervals (ARI), an index of ventricular repolarization, was determined from the epicardial ECG. The difference between the longest and shortest ARI was defined as ARI dispersion. RE-SULTS: Ischemic zone in atenolol group was less than that of control group (13 % ± 2 % vs 19 % ± 3 % , P - 0.04). In the control group, pooled ARI dispersion was increased by (18 ± 21), (27 ± 21), and (16 ± 10) ms at 30, 60, and 90 min of coronary artery occlusion respectively (P < 0.01), whereas in the atenolol group, ARI dispersion was only increased by (6 ± 4),     

小檗碱对肾性高血压心肌肥厚模型大鼠左心室重塑的影响

The purpose of this study is to evaluate the effects and the underline mechanisms of berberine on the cardiac function and left ventricular remodeling in rats with renovascular hypertension. The renovascular hypertensive model was established by the two-kidney, two-clip （2K2C） method in Sprague-Dawley （SD） rats. Two weeks after surgery, all the operated SD rats were randomly assigned into four groups： （1） renovascular hypertensive model group; （2） berberine 5 mg · kg^-1 group; （3） berberine 10 mg · kg^-1 group ; （4） captopril 45 mg · kg^-1 group ; and the sham operated rats were used as control. Four weeks after the drugs were administered, the cardiac function was assessed. The ratios of heart weight to body weight （HW/BW）, left ventricular weight to body weight （LVW/BW） and right ventricular weight to body weight （RVW/BW） were compared between groups. Coronal sections of the left ventricular tissue （LV） were prepared for paraffin sections, picrosirius red and HE staining was performed. The left ventricular wall thickness （LVWT）, interventricular septal thickness （IVST）, the parameters of myocardial fibrosis indicated by interstitial collagen volume fraction （ICVF） and perivascular collagen area （ PVCA ） were assessed. Nitric oxide （ NO ）, adenosine cyclophosphate （ cAMP ） and guanosine cyclophosphate （cGMP） concentrations of left ventricular tissue were measured. Berberine 5 mg· kg^-1 and 10 mg · kg^-1 increased the left ventricular± dp/dt max. and HR. Berberine 10 mg · kg^-1 decreased HW/BW and LVW/BW. The image analysis showed that both 5 and 10 mg · kg^-1 of berberine decreased LVWT, ICVF and PVCA, while increased the NO and cAMP contents in left ventricular tissue. Berberine could improve cardiac contractility of 2K2C model rats, and inhibit left ventricular remodeling especially myocardial fibrosis in renovascular hypertension rats. And such effects may partially associate with the increased NO and cAMP content in left ventricular tissue.     

川芎嗪对麻醉犬心血管作用的初步观察

Tetramethylpyrazine (TMPZ) has been shown to be one of the active principles of the Chinese medicinal plant "Chuan Qong", Ligusticum Wallichii Franch.TMPZ (4, 8 or 16 mg/kg) given intravenously to anesthetized dogs transiently decreased the blood pressure and markedly increased the heart rate and maximal rate of the left ventricular pressure. These cardiovascular effects of TMPZ seemed to be dosedependent. Prior administration of propranolol (2 mg/kg, I. V.) abolished the effect of TMPZ on the heart, leaving the depressor effect of TMPZ unchanged. Reserpinization of the dog affected the cardiovascular actions of TMPZ in a way similar to propranolol. The cardiovascular responses to TMPZ still persisted after cervical vagotomy. The injection of TMPZ at a dose of 0.4～2 mg/kg into the vertebral artery induced no significant hemodynamic response.These results indicate that in the anesthetized dog TMPZ exhibited positive inotropic and chronotropic effects on the heart mediated by sympatho-adrenergic mechanism. In addition, TMPZ seemed to have some direct dilating action on the peripheral bloodvessels.     

Capsaicin facilitates carotid sinus baroreceptor activity in anesthetized rats

AIM: To study the effect of capsaicin on carotid sinus baroreceptor activity (CBA). METHODS: The functional curve of carotid baroreceptor (FCCB) was constructed and the functional parameters of carotid sinus baroreceptor were measured by recording sinus nerve afferent discharge in anesthetized rats with perfused isolated carotid sinus. RESULTS: Low-concentration of capsaicin (0.2 μmol/L) had no significant effect on CBA, while perfusion of the isolated carotid sinus with middle-concentration of capsaicin (1 μmol/L) could shift FCCB to the left and upward, with peak slope (PS) increased from (2.47 %±0.14 %)/mmHg to (2.88 %±0.10 %)/mmHg (P<0.05) and peak integral value of carotid sinus nerve discharge (PIV) enhanced from 211 %±5 % to 238 %±6 % (P<0.01). The threshold pressure (TP) and saturation pressure (SP) were significantly decreased from 68.0±1.1 to 62.7±1.0 mmHg (P<0.01) and from 171.0±1.6 to 165.0±0.6 mmHg (P<0.01). By perfusing with high-concentration of capsaicin (5μmol/L), FCCB was shi