Abstract. The status of nitric oxide (NO) in spontaneously hypertensive rats (SHR) is unclear and its bioavailability may be affected by imbalance with reactive oxygen species. We studied cardiovascular effects of an NO donor, pentaerythrityl tetranitrate (PETN) in SHR. We used Wistar rats, SHR and SHR treated with PETN (100 mg/kg/day). After six weeks, myocardium and aorta from each group were taken for biochemical and iliac artery for functional and morphological study. Long-term administration of PETN to SHR increased cGMP level in platelets and did not affect blood pressure. In myocardium, the therapy resulted in a decrease in cardiac hypertrophy and MDA level, and the increased antioxidant enzyme activity of superoxide dismutase (SOD) and glutathione peroxidase (GPx). In aorta, PETN decreased the NO-synthase activity and had no affect on the enzyme activities of SOD and GPx or on MDA level. In the iliac artery, the endothelium-dependent relaxation to acetylcholine was slightly improved and the maximum vasoconstriction to noradrenaline was decreased. Wall thickness, cross-sectional area, inner diameter, and wall thickness/ inner diameter measured after perfusion fixation (120 mmHg) were not affected. The small effect of PETN on cardiovascular system suggests that NO deficiency is probably not the main cause of pathological alterations in SHR.

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The authors studied the effects of a combination of pentoxifylline and nimodipine on cerebral lipid peroxidation in postischemic rat brain. Pentoxifylline (40 mg/kg) and nimodipine (3 mg/kg) were administered per os 30 min before 5 min of ischemia (four-vessel occlusion model of transient ischemia). The extent of peroxidation in brain tissue (cerebral cortex, hippocampus, striatum) was then estimated by assay of thiobarbituric acid reactive substances (TBARS). The concentration of TBARS was significantly lower in the cerebral cortex and hippocampus of the group treated with the combination of drugs than in untreated ischemic rats. However, this concentration was not significantly different from that found in the cerebral cortex and hippocampus of other groups premedicated with nimodipine or pentoxifylline alone. The tested drugs had no effect on TBARS in the striatum. The hypothesis that the combination of drugs would have a synergistic effect on postischemic lipid peroxidation was therefore not confirmed.

The pharmacokinetics of two beta adrenoceptor blocking drugs, exaprolol and propranolol, in rats with interrupted enterohepatic circulation was studied. The tritium-labelled drugs were given intravenously to four groups of rats: control, bile-duct cannulated, bile-duct ligated, and pretreated with neomycin. Plasma levels and excretion were observed up to 96 h after administration. The pharmacokinetic parameters show an enhanced plasma elimination of both drugs at interrupted enterohepatic circulation compared to the control group. Significant changes were observed in the excretion pattern with bile-duct cannulated and bile-duct ligated rats, while the total radioactivity excreted in urine and faeces does not differ between control and neomycin pretreated rats.

The pharmacokinetics of pentacaine, a new local anaesthetic agent from the group of carbanilates, was investigated in the rat at a dose of 2 mg kg-1 i.v. and per os. A three-compartment open model gave the best fit to the data. The model parameters are: t1/2 99.0 +/- 14.1 min, Vss 7411.1 ml kg-1, Cl 77.9 ml min-1 kg-1; after oral administration t1/2ab 4.9 +/- 1.9 min, bioavailability 59.1 per cent, and extent of absorption 79.3 per cent. Pentacaine is eliminated almost entirely by metabolism. The metabolites are excreted equally in the urine and faeces at a relatively slow rate. The pharmacokinetics of pentacaine was linear in the dose range 0.008-4 mg kg-1. The whole-body autoradiography in mice showed rapid transfer of 3H radioactivity from the vessels to tissues and a markedly heterogeneous disposition pattern in organs.