1. Myocardial hypertrophy is a common pathologicalchange that accompanies cardiovascular disease. Dopamine D2receptors have been demonstrated in cardiovascular tissues.However, the pathophysiological involvement of D2 receptorsin myocardial hypertrophy is unclear. Therefore, the effects ofthe D2 receptor agonist bromocriptine and the D2 receptorantagonist haloperidol on angiotensin (Ang) II-or endothelin(ET)-1-induced hypertrophy of cultured neonatal rat ventricularmyocytes were investigated in the present study.2. Protein content and protein synthesis, determined byexamining [3H]-leucine uptake, were used as estimates of cardiomyocytehypertrophy. The expression of D2 receptor proteinin neonatal rat ventricular myocytes was determined usingwestern blotting. Changes in [Ca2?]i in cardiomyocytes wereobserved by laser scanning confocal microscopy.3. Angiotensin II and ET-1, both at 10 nmol/L, inducedmyocyte hypertrophy, as demonstrated by increased proteincontent and synthesis, [Ca2?]i levels, protein kinase C (PKC)activity and phosphorylation of extracellular signal-regulatedkinase, c-Jun N-terminal kinase and mitogen-activated proteinkinase (MAPK) p38 (p38). Concomitant treatment of cells with10 nmol/L AngII plus 10mol/L bromocriptine significantlyinhibited cardiomyocyte hypertrophy, MAPK phosphorylationand PKC activity in the membrane, as well as [Ca2?]i signallingpathways, compared with the effects of AngII alone. In addition, 10 mol/L bromocriptine significantly inhibited cardiomyocytehypertrophy induced by 10 nmol/L ET-1. However, pretreatmentwith haloperidol (10mol/L) had no significant effects oncardiomyocyte hypertrophy induced by either AngII or ET-1.4. In conclusion, D2 receptor stimulation inhibits AngIIinducedhypertrophy of cultured neonatal rat ventricularmyocytes via inhibition of MAPK, PKC and [Ca2?]i signallingpathways.

The effects of artemisin in on the potassium ionic currents of guinea pig ventricular cells and dog Purkinje fibres were studied using the whole cell voltage clamp technique. Artemisin in significantly decreased inward rectifier K+ current (IK1) with an IC50 of (7. 2

AIM: To study the effects of berberine on inward rectifier potassium current (Ik1) and outward delayed rectifier potassium current (Ik) of guinea pig ventricular my ocytes, and on human ether-a-go-go related gent (HERG) channel expressed in Xenopus oocytes. METHODS: Whole cell patch-clamp and geneclamp techniques were used to record ionic currents.RESUTS: Berberine prolonged action potential duration (APD) and inhibited Ik1 and Ik in a concentration-dependent manner. Berberine 100μmo1/L increased APD90 from (450±48) ms to (888±90) ms (n=6,P<0.01), and inhibited Ik1 by 64%±7%(n=6,P<0.01). Berberine 50μmo1/L inhibited Ik by 57%±6%,Iktmil by 52%±6%(n=6,P<0.01). Berberine produced a voltage-dependent block on Ik that increased with stronger depolarization, and once all channels activated, there was no further block at positive potentials. Berberine blocked the HERG channels potently with an IC50 value of approximately 75μmo1/L. This block was voltage-dependent, suggesting that it probably bind to either open or inactivated HERG channels. CONCLUSION: Berberine prolonged APD and possessed blocking effect on Ik1,Ik, and HERG channel expressed in Xenopus oocytes. The antiarrhythmic mechanism of berberine is related to its inhibitory effects on Ik1,Ik,and HERG channel.

Calcium sensing receptors (CaSR) is a member of super-family of G-protein coupling receptors.This review first introduced the concept, construction features, distribution, functions, decision methods, moderators, ge-netic locus of CaSR and its relationship with some diseases concisely. Then this article described the investigation progressof CaSR in cardiovascular system intensively, including the expression pattern, role and signal pathways of CaSR in rat my-ocardium in normal, ischemia-reperfusion injury, apoptosis and cardiac hypertrophy; the role and mechanism of CaSR incalcium homostasis regulation of rat myocardium, endoplasmic reticulum (ER) stress and cardiac ischemic preconditioningand postconditioning. The metabolism rule, physiological significance and pathological action of polyamine in cardiac cells; the increase of CaSR expression in cardiac tissue of artherosclerosic rat and its effect on sensitivity to acute myocardial in-farction are also discussed. In the end, the research perspective of CaSR in cardiovascular system was anticipated.

Polyamines (putrescine, spermidine and spermine) are essential for cell growth and differentiation. Nitric oxideexhibits antihypertrophic functions and inhibits cardiac remodelling. However, the metabolism of polyamines and thepotential interactions with nitric oxide in cardiac hypertrophy remain unclear. We randomly divided Wistar rats into fourtreatment groups: controls, isoproterenol (ISO), ISO and -arginine, and -arginine. Isoproterenol (5mg/kg/day, subcutaneously)and/or?-arginine (800 mg/kg/day, intraperitoneally) was administered once daily for 7 days. The expression ofatrial natriuretic peptide mRNA was determined by reverse transcription-polymerase chain reaction, and fibrogenesis ofheart was assessed by Van Gieson staining. Polyamines were measured with high-performance liquid chromatography, andplasma nitric oxide content and lactate dehydrogenase (LDH) activity were determined with a spectrophotometer. Theexpression levels of ornithine decarboxylase, spermidine/spermine N1-acetyltransferase (SSAT), endothelial nitric oxidesynthase (eNOS) and inducible nitric oxide synthase (iNOS) were analysed by Western blot. Heart-to-body weight ratio,left ventricle-to-body weight ratio, atrial natriuretic peptide mRNA expression, collagen fibres and LDH activity wereelevated, both ornithine decarboxylase and SSAT proteins were up-regulated, and total polyamines were increased in thegroup treated with ISO. Additionally, the expression of iNOS was up-regulated, eNOS was down-regulated, and nitricoxide levels were low. Notably, cotreatment with -arginine reversed most of these changes except for SSAT expression,which was further up-regulated. We propose that increased polyamines and decreased nitric oxide are involved in cardiachypertrophy induced by ISO and suggest that -arginine pre-treatment can attenuate cardiac hypertrophy through theregulation of key enzymes of the polyamine and nitric oxide pathways.