Calcium channel blockers increase the amount of nitrite production in rabbits without decreasing the responsiveness of platelets to collagen.

By virtue of their ability to increase nitric oxide (NO) production, it is thought that calcium channel blockers (CCBs) may be involved in the inhibition of platelet aggregation. In an attempt to compare the abilities of different groups of calcium antagonists to affect NO generation and platelet aggregation, single doses of the calcium antagonists verapamil, nicardipine and diltiazem were administered to rabbits. It was found that each of these drugs increased the levels of nitrite significantly. It was also found that these drugs had different time courses of action. Of the CCBs used in this study, verapamil was found to induce the greatest increase in nitrite production (about a 4-fold increase over basal levels), peaking at 90 min (P<0.001). Diltiazem and nicardipine (3.5-fold and 2.5-fold increase over basal levels, respectively) were both found to induce increases in NO which peaked at 150 min (P<0.001 and P<0.01 respectively). Each of the drugs was then given at double the original dose; however, nicardipine was the only drug that was seen to further increase nitrite production (P<0.001). Blood samples taken from the animals were analysed using whole-blood aggregometry in order to assess the amount of collagen-induced platelet aggregation. At the time point when NO release was expected to be maximal (150 min), it was found that the collagen-induced platelet responses were not significantly altered in platelets from rabbits that had been treated with either verapamil or nicardipine. In contrast, at the 150-min time point, diltiazem treatment made the platelets hypersensitive to collagen stimulation. The results of this study demonstrate that treatment with calcium channel antagonists increases the levels of NO produced in rabbits, however, this increase in NO production is not accompanied by a decrease in the reactivity of platelets to collagen.

The effects of verapamil on stress- and histamine-induced gastric lesions in rats.

The influence of verapamil on stress-induced and histamine-induced gastric ulcers was investigated in rats. The influence of verapamil was also examined on various biochemical parameters that affect the development of these ulcer models. The animals were pretreated with intraperitoneal verapamil (1, 5, 25 mg/kg) by injection 1 h before the induction of experimental ulceration. The gastric lesions were induced by cold-restraint stress or intraperitoneal injection of histamine (300 mg/kg). The gastroprotective effects of verapamil were evaluated by determining the ulcer index, gastric mucus content, free and total acidity, lipid peroxidation and non-protein sulfhydryl content. Verapamil pretreatment at a dose of 25 mg/kg significantly reduced stress-induced ulcers. Verapamil enhanced mucus secretion, reduced total acidity and lipid peroxidation and decreased non-protein sulfhydryl content in a dose-dependent fashion. On the other hand, pretreatment with verapamil at any dose had no significant effect on histamine-induced ulcers. L-Arginine (L-A) (100 mg/kg) or L-nitroarginine (L-NNA) (100 mg/kg) were also injected i.p. to the animals 1 h before stress to test the role of nitric oxide (NO) in the mechanism of the gastroprotective activity of verapamil (25 mg/kg). The results suggested that verapamil stimulates gastric NO production, but the overproduction of NO worsens gastric ulcers. The effects of verapamil on experimentally induced ulcers may be related to its ability to induce biochemical alterations in the parameters measured in gastric tissue.

The effects of gender difference on monocrotaline-induced pulmonary hypertension in rats.

The present study aimed to compare the effect of gender difference on hemodynamic consequences in the development of monocrotaline (MCT)-induced pulmonary hypertension in rat. The effect of antioxidant enzyme systems on the development of pulmonary hypertension mediated by the phytotoxin MCT and the effect of gender on these antioxidant systems were also investigated. For this purpose, the right ventricular pressures (RVPs) and right ventricular/heart weight (HW) ratios were compared between groups and the glutathione (GSH) level and superoxide dismutase (SOD), catalase (CAT) and glutathione-S-transferase (GST) activities were determined in lung and liver tissue samples of rats. RVP and right ventricular/HW ratios significantly increased in the MCT group compared to the control group. In the MCT group, RVP was significantly higher in males than females. MCT-induced pulmonary hypertension resulted in decreased GSH level, decreased GST and SOD activities and increased CAT activity in lung and liver tissues of both male and female rats. In addition, the lung and liver GSH level and GST and SOD levels were higher in female control rats compared to male control rats. The results of the present study, that antioxidant enzyme activities were different between the groups, highlight the possible role of oxidative stress in the pathogenesis of MCT-induced pulmonary hypertension in rats. Moreover, the lower antioxidant defense capacity of male rats than female rats may be considered as a cause of more aggressive course of MCT-induced pulmonary hypertension in males compared to females.

The effects of gender difference on monocrotaline-induced pulmonary hypertension in rats.

The present study aimed to compare the effect of gender difference on hemodynamic consequences in the development of monocrotaline (MCT)-induced pulmonary hypertension in rat. The effect of antioxidant enzyme systems on the development of pulmonary hypertension mediated by the phytotoxin MCT and the effect of gender on these antioxidant systems were also investigated. For this purpose, the right ventricular pressures (RVPs) and right ventricular/heart weight (HW) ratios were compared between groups and the glutathione (GSH) level and superoxide dismutase (SOD), catalase (CAT) and glutathione-S-transferase (GST) activities were determined in lung and liver tissue samples of rats. RVP and right ventricular/HW ratios significantly increased in the MCT group compared to the control group. In the MCT group, RVP was significantly higher in males than females. MCT-induced pulmonary hypertension resulted in decreased GSH level, decreased GST and SOD activities and increased CAT activity in lung and liver tissues of both male and female rats. In addition, the lung and liver GSH level and GST and SOD levels were higher in female control rats compared to male control rats. The results of the present study, that antioxidant enzyme activities were different between the groups, highlight the possible role of oxidative stress in the pathogenesis of MCT-induced pulmonary hypertension in rats. Moreover, the lower antioxidant defense capacity of male rats than female rats may be considered as a cause of more aggressive course of MCT-induced pulmonary hypertension in males compared to females.

The effect of combination therapy on the plasma concentrations of traditional antiepileptics: a retrospective study.

The present study aimed at determining the differences in plasma concentrations of traditional antiepileptics such as phenytoin, carbamazepine, and valproic acid in patients receiving monotherapy and combination therapy. In addition, the effect of gender and age on plasma drug concentration was evaluated in these patients. For this purpose, plasma trough concentrations obtained during routine therapeutic monitoring of these drugs were assessed retrospectively. The average plasma concentrations reached the apparent therapeutic ranges, except for the average plasma concentration of phenytoin, which was below the therapeutic range in patients who received only phenytoin or in combination with the other agents. Phenytoin when combined with carbamazepine or valproic acid significantly decreased the average plasma concentrations of these drugs to subtherapeutic concentrations. The results showed that plasma carbamazepine concentrations were higher in men than in women, whereas plasma concentrations of valproic acid and phenytoin were higher in women than in men. The difference in this regard between men and women was found to be statistically significant for phenytoin. The difference between the average plasma concentrations of carbamazepine, phenytoin, and valproic acid among age groups was not significant. In conclusion, our study measured the average plasma antiepileptic drug concentrations in patients with epilepsy who were receiving monotherapy and combination therapy and were routinely monitored, and has thus shown the importance of drug monitoring in the evaluation of the effectiveness of these drugs.

Studies on calcium antagonist activities of 2-ethyl-3-carbmethoxy-4-aryl- 5-oxo-6,6-dimethyl-1,4,5,6,7,8-hexahydroquinoline derivatives.

In this study, 23 new compounds having 2-ethyl-3-carbmethoxy-4-aryl-5-oxo-6,6-dimethyl-1,4,5,6,7, 8-hexahydroquinoline structure have been synthesised and screened for their calcium antagonistic activities. The structure of the compounds were characterised by IR, 1H-NMR, 13C-NMR, mass spectroscopy and elemental analyses. The calcium antagonistic activities of the compounds were determined by the tests performed on isolated rat ileum and lamb carotid artery. Although none of the synthesized compounds were as active as nicardipine in isolated rat ileum, the compounds 9, 10 and 19 have shown high activity. In screening studies on lamb carotid artery, compounds 10, 14 and 19 have been found active at a concentration of 10(-4) mol/l.

Electromagnetic waves of 900 MHz in acute pentylenetetrazole model in ontogenesis in mice.

The purpose of this study was to measure the effects of electromagnetic waves (EMW) at 900 MHz. EMW were produced by a signal generator and were administered to mice via an antenna. The frequency of the waves was tested by a spectrum analyser and a frequency-meter. The emitted power was 0.25 mW. A total of 117 mice (59 prepubertal and 58 adult) was used. Mice were exposed to EMW or sham radiation for 2 h and 20 h before an injection of pentylenetetrazole (PTZ). A statistically significant difference was found between the latency measurements within 20 h for prepubertal mice in stages 1 and 2 ( p<0.05). The effects on prepubertal mice of long-term 900 MHz EMW in a PTZ model may be an indication of possible problems in developing brains.