The Effect of Sumatriptan in Ischemic Conditions in the Rat Heart.

OBJECTIVES: The aim of this study was to investigate the effect of SUM on IR-induced injury in rat heart and its effect on IPC-induced protection. MATERIALS AND METHODS: The rats were randomly divided into four groups: IR, SUM-IR, IPC, and SUM-IPC. The mean arterial blood pressure and heart rate were recorded to calculate PRP. Standard limb lead 2 ECG were recorded to evaluate arrhythmia parameters. RESULTS: The PRP values in the SUM-IPC group were significantly lower than in the SUM-IR group at the beginning of reperfusion (p<0.05). The incidence of VT in the IPC, SUM-IR, and SUM-IPC groups was significantly lower than in the IR group (p<0.05). VF was only observed in the IR group. CONCLUSION: SUM protects the heart against IR injury but is not as protective as IPC alone. Although SUM diminishes IPC-induced protection against VT, the preventive effect of SUM against VF may be predictive for cardioprotection in ischemic conditions.

Endothelial nitric oxide synthase gene polymorphism in gastric cancer.

BACKGROUND/AIMS: Nitric oxide, a labile compound synthesized by nitric oxide synthase, is a major regulator not only of physiological vascular tonus but also of the abnormal vascularity associated with tumors. Endothelial production of nitric oxide regulates blood flow and angiogenesis and reduces tumor cell adhesion to the endothelium. A high concentration of nitric oxide and its metabolites causes DNA damage during nitration, nitrosation and deamination. Both positive and negative effects on carcinogenesis and tumor growth, apoptosis, and cytotoxic mechanisms may be explained by differential susceptibility of tumor cells to nitric oxide-mediated reactions. METHODS: In this study, three major polymorphisms (786T>C, the 27 base pair variable number of tandem repeats in intron 4, and 894G>T) of the endothelial nitric oxide synthase gene were investigated in gastric cancer and normal tissues of 50 patients with gastric cancer and in the peripheral blood of 98 healthy subjects. RESULTS: We found no significant differences in intron 4a/b and 894G>T (Glu298Asp) allele and genotype frequencies between control and patient specimens. Nevertheless, the genotype and allele frequencies of 786T>C polymorphism were found to be significantly different between the healthy controls and tumor tissues. CONCLUSIONS: The results suggest that endothelial nitric oxide synthase 786T>C polymorphism may play a role in the development of gastric cancer.

The bactericidal and morphological effects of peroxynitrite on Helicobacter pylori.

Peroxynitrite (ONOO-) is correlated with the pathogenesis of Helicobacter pylori-induced peptic ulcer diseases. We aimed to investigate the time- and concentration-dependent bactericidal and morphological effects of ONOO- on H. pylori. Authentic ONOO- was synthesized as quenched-flow method. A stock culture of H. pylori NCTC 11637 was exposed to different concentrations of ONOO- (0.1-40 micromol/L) or decomposed ONOO- or fresh medium. Samples were taken at 0, 15, 30, 60, and 120 minutes, for the evaluation of viable bacteria and bacterial morphology with gram strain and transmission electron microscopy. Decomposed ONOO- showed no bactericidal activity against H. pylori. ONOO- application caused a decrease in the number of viable bacteria within the first 15 minutes. The significant conversion of H. pylori from spiral form to coccoid form was determined with 10 micromol/L of ONOO-, and higher concentrations caused lysis of the cells. Separation of cell wall, bleb formation, vacuolization, decrease of secretory granules, and lysis of bacteria were the morphological effects of ONOO- on H. pylori. Because the morphology of the bacteria is one of the important factors in virulence; peroxynitrite-related morphological effects might have an impact in the progress of the H. pylori-induced peptic ulcer diseases.

Angiotensin II captopril cotreatment augments angiogenesis in abdominal skin flap in rats.

The effect of captopril, angiotensin-converting enzyme inhibitor, on angiogenesis in several reports remained unclear. Its effect on neovascularization in rat abdominal skin flaps was investigated. Flap elevation, based on the right superficial inferior epigastric artery was performed with or without the administration of captopril (10 mg/kg/d), Ang II (100 microg/kg/d), or captopril and Ang II cotreatment. Mean arterial pressure (MAP), microangiography, capillary density measurement, necrosis area determination, laser Doppler flowmetry (LDF), AT1 and vascular endothelial growth factor (VEGF) immunostaining were used to evaluate the effects of captopril and the interaction between captopril and Ang II on the angiogenesis. Ang II and captopril cotreatment improved angiogenesis more than Ang II or captopril alone. The reduction of necrosis, enhancement of vascular network formation, capillary density, VEGF immunostaining, and local blood flow were evident in the cotreated group. We suggest that Ang II and captopril cotreatment improves ischemia-induced angiogenesis and increased viability and vascularity of skin flap in rats.

Peroxynitrite in reperfusion arrhythmias and its whole blood chemiluminescence results.

The aims of the present study were to investigate the effects of exogenous peroxynitrite (ONOO(-)) on reperfusion arrhythmias in anaesthetized rats, and to detect endogenous and exogenous ONOO(-)-induced chemiluminescence (CL) signals in rat whole blood, which was collected during baseline and in the first minute of reperfusion. ONOO(-) infusion in ischemia/reperfusion (I/R) applied groups caused significant decreases in mean arterial pressure (MAP) and heart rate (HR). Ventricular fibrillation (VF) incidences in the vehicle, ONOO(-), and dec-ONOO(-) infused groups were 63, 100, and 20%, respectively. In control group CL signal was 136+/-34mV during the resting period and was increased to 336+/-57mV with reperfusion. Also, the effects of SOD+CAT, L-NAME and urate were investigated. Ventricular tachycardia (VT) incidence was decreased significantly in SOD+CAT and urate; VF incidence was decreased significantly in SOD+CAT applied groups. CL signals were inhibited with SOD+CAT, L-NAME, and urate. Exogenous ONOO(-) infusion during I/R was also investigated. CL signal in exogenously ONOO(-) infused group is increased 423% during reperfusion. Only urate infused group VF incidence was decreased significantly. CL signals of ONOO(-) infused groups were inhibited by SOD+CAT, L-NAME, and urate. Based on the results of the current study, ONOO(-) seems to be one of the key mediators of reperfusion arrhythmias in anaesthetized rats.

Contractile responses of the human umbilical artery to KCl and serotonin in Ca-free medium and the effects of levcromakalim.

It is known that K(ATP) channel openers inhibit the release and refilling of Ca(2+) from intracellular stores. The present study was designed to test the effects of levcromakalim in human umbilical artery (HUA) rings stimulated by serotonin (5-HT) and KCl in Ca-free medium. Umbilical cords were obtained at vaginal or cesarean deliveries from healthy, term pregnancies. After the isolation, HUA rings were placed in organ baths in solution with indomethacin (10(-5) M) and N(G)-nitro-L-arginine methyl ester (L-NAME) (10(-3) M) at 37 degrees C and aerated with 95% O(2) and 5% CO(2) for the measurement of isometric force. In Ca-free solution with Ethylene glycol-bis (ss-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) (2 mM) the contractions produced by 5-HT (10(-6) M) and KCl (40 mM) decreased significantly. Afterwards, HUA rings were treated with 5-HT and KCl in repeated manner in Ca-free medium. In contrast to KCl, 5-HT induced contractions reduced in each application, progressively. Levcromakalim (10(-4) M) abolished the contractions elicited by 5-HT. On the other hand, levcromakalim had a little but significant inhibitory effect on KCl induced contraction in Ca-free medium. These results suggest that Ca(2+) is not the only transduction pathway in KCl produced contractions of HUA smooth muscle cells.