Relaxation Patterns of Human Gastric Corporal Smooth Muscle by Cyclic Nucleotides Producing Agents

To elucidate the mechanism of cyclic nucleotides, such as adenosine 3',5'-cyclic monophosphate (cAMP) and guanosine 3',5' -cyclic monophosphate (cGMP), in the regulation of human gastric motility, we examined the effects of forskolin (FSK), isoproterenol (ISO) and sodium nitroprusside (SNP) on the spontaneous, high K+ and acetylcholine (ACh)-induced contractions of corporal circular smooth muscle in human stomach. Gastric circular smooth muscle showed regular spontaneous contraction, and FSK, ISO and SNP inhibited its phasic contraction and basal tone in a concentration-dependent manner. High K+ (50 mM) produced sustained tonic contraction, and ACh (10 micrometer) produced initial transient contraction followed by later sustained tonic contraction with superimposed phasic contractions. FSK, ISO and SNP inhibited high K+-induced tonic contraction and also ACh-induced phasic and tonic contraction in a reversible manner. Nifedipine (1 micrometer), inhibitor of voltage-dependent L-type calcium current (VDCC(L)), almost abolished ACh-induced phasic contractions. These findings suggest that FSK, ISO and SNP, which are known cyclic nucleotide stimulators, inhibit smooth muscle contraction in human stomach partly via inhibition of VDCCL.

Regulation of Ba2+-Induced Contraction of Murine Ureteral Smooth Muscle

This study was designed to characterize ureteral smooth muscle motility and also to study the effect of forskolin (FSK) and isoproterenol (ISO) on smooth muscle contractility in murine ureter. High K+ (50 mM) produced tonic contraction by 0.17+/-0.06 mN (n=19). Neuropeptide and neurotransmitters such as serotonin (5microM), histamine (20microM), and carbarchol (CCh, 10~50microM) did not produce significant contraction. However, CCh (50microM) produced slow phasic contraction in the presence of 25 mM K+. Cyclopiazonic acid (CPA, 10microM), SR Ca2+-ATPase blocker, produced tonic contraction (0.07 mN). Meanwhile, inhibition of mitochondria by protonophore carbnylcyanide m-chlorophenylhydrazone (CCCP) also produced weak tonic contraction (0.01 mN). The possible involvement of K+ channels was also pursued. Tetraethyl ammonium chloride (TEA, 10 mM), glibenclamide (10microM) and quinidine (20 microM) which are known to block Ca2+-activated K+ channels (KCa channel), ATP-sensitive K+ channels (KATP) and nonselective K+ channel, respectively, did not elicit any significant effect. However, Ba2+ (1~2 mM), blocker of inward rectifier K+ channels (KIR channel), produced phasic contraction in a reversible manner, which was blocked by 1microM nicardipine, a blocker of dehydropyridine-sensitive voltage-dependent L-type Ca2+ channels (VDCCL) in smooth muscle membrane. This Ba2+-induced phasic contraction was significantly enhanced by 10microM cyclopiazonic acid (CPA) in the frequency and amplitude. Finally, regulation of Ba2+-induced contraction was studied by FSK and ISO which are known as adenylyl cyclase activator and beta-adrenergic receptor agonist, respectively. These drugs significantly suppressed the frequency and amplitude of Ba2+-induced contraction (p<0.05). These results suggest that Ba2+ produces phasic contraction in murine ureteral smooth muscle which can be regulated by FSK and beta-adrenergic stimulation.

Powdered injections of luotai protect against ISO-induced experimental myocardial ischemia model on rats / 中国临床药理学与治疗学

Aim Powdered injections of luotai consist of total saponins of panax notoginseng(PNS) which protect against ischemia injury from myocardial reperfusion injury.Methods ISO-induced acute myocardial ischemia model in rat was made, which decreased S-T sigments in ECG.Luotai after intravenous injection or oral can protect against S-T sigment significant reduction and ∑ST after ISO induced acute myocardial ischemia .Results Luotai 50 mg?kg-1 and 100 mg?kg-1 significantly inhibited S-T sigment decreases. Conclusion Luotai protect ISO induced acute myocardial ischemia and has dose-dependent effect.This ISO-induced acute myocardial ischemia model in rat has some significant advantages,for example,higher stability, good duplication, quickly filtrates, easily masters.

Protective effect of crocetin on isoproterenol-induced myocardial injury in rats / 中草药

Object To study the protective effect of crocetin on myocardial ischemia induced by isoproterenol (ISO). Methods Myocardial ischemia was induced by subcutaneous injection of ISO (30 mg/kg for two days, once a day). The experimental animals were randomly divided into the normal group, ISO group, positive control group and three crocetin groups (25, 50, 100 mg/kg). Cardiac indexes were examined. The level of LDH, CK, MDA in serum were measured. The content of MDA, GSH-Px and the ATPase activity heart and mitochondria were assayed by colorimetric analysis. The histopathological change of myocardia was investigated by HE staining. Results Compared with the model group, crocetin can significantly reduce the cardiac indexes, obviously decrease the level of MDA, LDH and CK in the serum. Crocetin can significantly increase the activities of Na +, K +-ATPase; Ca 2+ , Mg 2+ -APTase; GSH-Px. The histopathological changes confirmed the protective effects of crocetin on the myocardial injury. Conclusion Crocetin could alleviate the acute myocardial ischemia induced by ISO in rats.