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.

This study was focused on investigating the involvement of polyamine metabolism in the myocardial ischemia-reperfusion injury (MIRI)in an in vivo rat model. A branch of the descending left coronary artery was occluded for 30 min followed by 2 h, 6 h, 12 h, and 24 hreperfusion. Then the expression of spermidine/spermine N1-acetyltransferase (SSAT) and ornithine decarboxylase (ODC) and theconcentrations of polyamines were assessed. It was found that the expression of SSAT and ODC were upregulated after reperfusion and theconcentrations of spermidine and spermine were significantly decreased, while putrescine concentration was significantly increased. Theresults suggest that MIRI may cause disturbance of polyamine metabolism, and it may play a critical role in MIRI

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.

The intracellular Ca2? concentration ([Ca2?]i) isincreased during cardiac ischemia/reperfusion injury (IRI),leading to endo(sarco)plasmic reticulum (ER) stress. PersistentER stress, such as with the accumulation of [Ca2?]i,results in apoptosis. Ischemic post-conditioning (PC) canprotect cardiomyocytes from IRI by reducing the [Ca2?]i via protein kinase C (PKC). The calcium-sensing receptor(CaR), a G protein-coupled receptor, causes the productionof inositol phosphate (IP3) to increase therelease of intracellular Ca2? from the ER. This processcan be negatively regulated by PKC through the phosphorylationof Thr-888 of the CaR. This study testedthe hypothesis that PC prevents cardiomyocyte apoptosisby reducing the [Ca2?]i through an interaction of PKCwith CaR to alleviate [Ca2?]ER depletion and [Ca2?]melevation by the ER-mitochondrial associated membrane(MAM). Cardiomyocytes were post-conditioned after 3 hof ischemia by three cycles of 5 min of reperfusion and5 min of re-ischemia before 6 h of reperfusion. DuringPC, PKCe translocated to the cell membrane and interactedwith CaR. While PC led to a significant decreasein [Ca2?]i, the [Ca2?]ER was not reduced and [Ca2?]mwas not increased in the PC and GdCl3–PC groups.Furthermore, there was no evident Dwm collapse duringPC compared with ischemia/reperfusion (I/R) or PKCinhibitor groups, as evaluated by laser confocal scanningmicroscopy. The apoptotic rates detected by TUNEL andHoechst33342 were lower in PC and GdCl3–PC groupsthan those in I/R and PKC inhibitor groups. Apoptoticproteins, including m-calpain, BAP31, and caspase-12,were significantly increased in the I/R and PKC inhibitorgroups. These results suggested that PKCe interactingwith CaR protected post-conditioned cardiomyocytes fromprogrammed cell death by inhibiting disruption of themitochondria by the ER as well as preventing calciuminducedsignaling of the apoptotic pathway.

The expression and function of calcium-sensingreceptor (CaSR) in differentiated THP-1 (human acutemonocytic leukemia cell line) cells are unknown currently.This study investigated above-mentioned issues usingTRAP staining, immunofluorescence staining, Westernblotting, ELISA, and Laser Confocal Scanning Microscopytechniques. We found that CaSR protein was expressed, andmainly located in the membrane and cytoplasm in differentiatedTHP-1 cells. Elevated extracellular calcium orGdCl3 (an agonist of CaSR) raised intracellular calciumconcentration. And this increase was inhibited or abolishedby NPS2390 (an inhibitor of CaSR), U73122 (a specificinhibitor of phospholipase C, PLC) or thapsigargin (a Ca2?-ATPase inhibitor). The extracellular GdCl3 elevation stimulatedboth of IL-1b and TNFa release, and this effect ofGdCl3 was inhibited by NPS2390. In conclusion, CaSR isfunctionally expressed in differentiated THP-1 cells, and theactivated CaSR contributes to intracellular calcium incrementthrough Gq-PLC-inositol triphosphate (IP3) pathwayand commits to cytokine secretion. These results suggestthat CaSR might be involved in a variety of pathologicalprocesses mediated by activated monocyte-macrophages.