Inhibitory effects of rosiglitazone against endothelin-1-induced proliferation of rat cardiac myocytes: the role of PKC-c-fos pathway / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the mechanism of rosiglitazone (RSG, the activator of peroxisome proliferators activated receptor lambda) for inhibiting endothelin-1 (ET-1)-induced neonatal rat cardiac myocyte hypertrophy and the role of protein kinase C (PKC) and c-fos.</p><p><b>METHODS</b>In vitro cultured neonatal rat cardiac myocytes were treated with ET-1, phorbol ester (PMA, the PKC activator), ET-1+RSG, ET-1+chelerythrine (che, the PKC inhibitor), PMA+RSG, or without treatment (control), respectively. The effects of RSG on the protein content, (3)H-leucine incorporation, PKC activity and C-fos protein expression were observed in the cardiac myocytes stimulated with ET-1 or PMA.</p><p><b>RESULTS</b>After two days of culture, the intracellular protein content in ET-1 group and PMA group were increased by 15% (339-/+15 microg/ml) and 13% (329-/+14 microg/ml) as compared with the control cells (290-/+13 microg/ml), respectively (P<0.01). Compared with the ET-1 group, cells treated with ET-1+10(-8) mol/L RSG, ET-1+10(-7) mol/L RSG, and ET-1+che showed decreased intracellular protein content by 10% (303-/+14 microg/ml, P<0.05), 12% (292-/+11 microg/ml, P<0.05), and 13% (291-/+12 microg/ml, P<0.01), respectively. The intracellular protein content in PMA+10(-7) mol/LRSG group was decreased by 10% (P<0.05) in comparison with the PMA group. RSG inhibited protein synthesis enhancement and increased (3)H-leucine incorporation induced by ET-1 and PMA, and antagonized the effects of ET-1 and PMA in promoting PKC activity and c-fos protein expression in the myocytes.</p><p><b>CONCLUSION</b>The inhibitory effect of RSG on ET-1- or PMA-induced myocyte hypertrophy is associated with PKC-c-fos pathway.</p>

Vasonatrin peptide attenuates the enhancement of electrically-induced intracellular calcium transient by isoproterenol in rat cardiac myocytes / 生理学报

The purpose of this study was to investigate the effects of vasonatrin peptide (VNP) on electrically-induced intracellular calcium ([Ca(2+)](i)) transient and mechanism of the effects in the cardiac myocytes. The [Ca(2+)](i) transient was measured with a fluoremetric method. The effects of HS-142-1, 8-Br-cGMP and methylene blue (MB) on [Ca(2+)](i) transient in cardiac myocytes were also determined. Isoproterenol (Iso) at 10(-10)~10(-6) mol/L augmented electrically-induced [Ca(2+)](i) transient dose-dependently, which was (13+/-8)% (P>0.05), (26+/-13)% (P< 0.05), (66+/-10)% (P<0.01), (150+/-10)% (P<0.01) and (300+/-25)% (P<0.01), respectively. These effects were blocked by an beta-adrenergic bloker propranolol (10(-6) mol/L). The effect of Iso (10(-8) mol/L) on [Ca(2+)](i) transient was attenuated in a dose-dependent manner by VNP at 10(-10)~10(-6) mol/L, which was (99+/-3)% (P>0.05), (96+/-2)% (P<0.05), (84+/-6)% (P<0.01), (66+/-3)% (P<0.01) and (62+/-3)% (P<0.01), respectively. 8-Br-cGMP (10(-7)~10(-3) mol/L) aslo attenuated 10(-8) mol/L Iso-induced [Ca(2+)](i) transient dose-dependent. The effect of VNP on [Ca(2+)](i) transient was almost abolished in the presence of HS-142-1 (2x10(-5) mol/L), an antagonist of the natriuretic peptide guanylate cyclase (GC) receptors. MB (10(-5) mol/L), an inhibitor of GC, not only blocked the effect of VNP in myocytes, but also augmented electrically-induced [Ca(2+)](i) transient. VNP and HS-142-1 themselves did not change the [Ca(2+)](i) transient in the cardiac myocytes significantly. But MB augmented the [Ca(2+)](i) transient in the cardiac myocytes significantly. These results suggest that VNP attenuates [Ca(2+)](i) transient induced by Iso. This effect is possibly achieved by binding VNP with the natriuretic peptide GC receptors in the myocytes, leading to an increase in intracellular cGMP.

Effect of anions and anion channel blockers on vascular tone in rat aorta / 中国应用生理学杂志

<p><b>AIM</b>To investigate the action of anions and anion channel blockers in the regulation of vascular contraction induced by norepinephrine (NE).</p><p><b>METHODS</b>NE-induced contraction was observed in rat aorta by using routine blood vascular perfusion in vitro.</p><p><b>RESULTS</b>The anion channel blockers niflumic acid (NFA) and 5-nitro-2-(3-phenoxylpropylamino)-benzoic acid (NPPB) produced inhibitory effects on NE-evoked contractions in the aorta. NE-induced contraction was not significantly changed after the extracellular Na+ was replaced by choline, in contrast, the vascular was relaxed when the extracellular Cl- was replaced by glutamate. Moreover, the vasoconstriction induced by NE was further enhanced with the replacement of the extracellular Cl- by Br-, which was still sensitive to either NFA or NPPB.</p><p><b>CONCLUSIONS</b>Anion channels play an important role in the regulation of blood vascular tone, which may be responsible for the salt-sensitivity hypertension.</p>

Kappa-opioid receptor stimulation contributes to aortic artery dilation through activation of K(ATP) channel in the rats / 生理学报

To investigate the relaxation effect and underlying mechanism of U50,488H (a selective kappa-opioid receptor agonist) on aorta in the rat, isolated aortic ring was perfused and the tension of the vessel was measured. It was shown: (1) kappa-opioid receptor stimulation with U50,488H relaxed rat aorta dose-dependently; (2) the relaxation effect of U50,488H on aorta was partially endothelium-dependent; (3) the relaxation effect of U50,488H was significantly attenuated in the presence of glybenclamide and glipizide, two ATP-sensitive K(+) channel (K(ATP)) blockers; and (4) the relaxation effect of U50,488H on vessel bore no relationship to muscarinic-receptor, beta-adrenoceptor, prostaglandin and nitric oxide (NO). These results indicate that kappa-opioid receptor stimulation with U50,488H relaxes the aortic artery at least partially via K(ATP) channel in the rat.

Effect of bradykinin on the sodium channel current in dorsal root ganglion neuron / 中国应用生理学杂志

<p><b>AIM</b>To investigate the effects of bradykinin on voltage-dependent sodium channel currents in rat dorsal root ganglion neurons (DRG).</p><p><b>METHODS</b>Whole-cell patch clamp technique was used to determine sodium channel current.</p><p><b>RESULTS</b>Bradykinin at 0.01 - 10.0 micromol/L dose dependently increased the frequency of repetitive firing of DRG. Bradykinin at 0.01 - 10.0 micromol/L dose dependently enhanced the TTX-R sodium current, and had no effect on TTX-S sodium current.</p><p><b>CONCLUSION</b>Mechanism underlying the inflammation induced by bradykinin is related to the TTX-R sodium channel.</p>