ABSTRACT
The purpose of the present study was to establish in the mini pig model the effects of paraoxon (POX) on PLA2 activity. Six anesthetized and mechanically ventilated mini pigs were infused over 50 min with 0.3, 1, 3, 9, 27 and 81 mg POX kg(-1) BW(-1) dissolved in ethanol, respectively. The control animal received no POX but the ethanol amount corresponding to the highest POX dose. PLA2 activity measurements were carried out immediately after POX application. Data were analysed with the Mann Whitney-Wilcoxon rank order test. Statistical significance was assumed for P < or = 0.05. Exposure to POX inhibited PLA2 activity to 50.5 +/- 8.9% of baseline activity. The changes seen were not dose-dependent. The dose dependency previously demonstrated in vitro was not reproducible in vivo. This is most probably due to the massive endogenous catecholamine release leading to PLA2 activation. An additional masking effect is due to the (co)administration of drugs needed for anesthesia and cardiovascular support, especially Mg2+. These substances also influence the PLA2 activity.
Subject(s)
Cholinesterase Inhibitors/toxicity , Paraoxon/toxicity , Phospholipases A/antagonists & inhibitors , Adrenal Glands/metabolism , Animals , Blood Platelets/enzymology , Catecholamines/metabolism , Dose-Response Relationship, Drug , Enzyme Activation , Ethanol/pharmacology , Infusions, Intravenous , Pharmaceutical Vehicles/pharmacology , Phospholipases A/blood , Phospholipases A2 , Reproducibility of Results , Swine , Swine, MiniatureABSTRACT
Dysregulation of the system of nitric oxide (NO)-cyclic 3',5'-guanosine monophosphate (cGMP) might be involved in the development of hypertension in transgenic hypertensive TGR(mREN2)27 (TGR) rats. The present study was performed to determine possible differences in the day-night pattern and the urinary excretion rates of NO and cGMP in TGR rats in comparison to normotensive Sprague-Dawley (SPRD) controls. In addition, the urinary excretion of creatinine and catecholamines was measured in both rat strains. The day-night excretion patterns of NO, cGMP, catecholamines, and creatinine were preserved in TGR rats. Urinary excretion of NO was significantly decreased in TGR rats, whereas cGMP, the second messenger of NO, was elevated in the transgenic animals. Catecholamines and creatinine excretion rates did not differ between the strains. In conclusion, data suggest that a reduced NO synthesis could contribute to the increased blood pressure in the severely hypertensive rats. However, these data make it unlikely that the disturbances in the nitric oxide-cGMP system and the sympathetic nervous system are mainly responsible for the inverse circadian blood pressure rhythm in TGR rats.
