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The ability of the clinically used cephalosporins: cephalothin, cefotaxime and cefotiam to induce lipid peroxidation (LPO) and renal damage was compared to that of nephrotoxic cephaloridine under in vivo conditions. Glutathione was measured in rat liver or in renal cortex as non-protein sulfhydryls. LPO was measured in plasma, renal cortex and liver by the generation of malondialdehyde or as the increase in renal cortical concentration of conjugated dienes. Impairment of renal function was measured as the decrease in renal cortical accumulation of the organic anion p-aminohippurate (PAH). Administration of cephalosporins to rats as a single dose (2000 mg/kg, ip) induced a significant glutathione-depletion in the renal cortex with cephaloridine, and in the liver with cephaloridine, cephalothin and cefotiam. Treatment of rats with cephaloridine, cephalothin and cefotiam (200, 500, or 1000 mg kg -1 day -1 , ip) for 5 days resulted in a dose-dependent increase of LPO in the renal cortex. While cephaloridine induced the highest concentration of conjugated diene, cefotaxime had no effect. Measurements of PAH accumulation in renal cortical slices from cephalosporin-treated rats showed a dose-dependent decrease in the renal cortical accumulation of PAH. Pretreatment with the antioxidants vitamin E or cyanidanol (400 mg kg -1 day -1 , ip) 1 h before treatment with cephaloridine, cephalothin or cefotiam (1000 mg kg -1 day -1 , ip) for 3 days inhibited cephalosporin-induced LPO and significantly reduced the impairment of renal cortical accumulation of PAH. The potential of different cephalosporins for inducing LPO and reducing PAH accumulation was ranked as follows: cephaloridine > cephalothin > cefotiam > cefotaxime.

Pulmonary hypertension (PH) is a chronic disabling disease that affects the pulmonary vasculature. In this study, we have examined the effect of blocking potassium channels on sympathetic neurotransmission in the pulmonary artery and how this is influenced by PH.The right ventricular pressure was 30.4±3.5 mmHg and 52.8±5.4 mmHg in control and hypertensive rats respectively. These values were significantly different from each other indicating pulmonary hypertension. Electrical stimulation of the pulmonary artery produced frequency‐dependent contractions with LogES50 values of 1.13±0.18 and 0.44±0.26 in control hypertensive rats, respectively. There was no significant difference in the maximum response between the groups. TEA (1 mM), a BKca channel blocker, produced a nonsignificant increase in maximum response in control rat but produced a significant shift of the frequency‐response curve to the left reducing the LogES50 value from 1.13±0.18 to 0.37±0.32 (n=5). In hypertensive rats TEA (1 mM) shifted the frequency‐response curve to the left and significantly increased the maximum response. It was concluded that BKCA channels modulated adrenergic transmission in the rat pulmonary artery and this was not affected by pulmonary hypertension.

Pulmonary hypertension (PH) is a chronic disabling disease that largely affects the pulmonary vasculature. In this study, we have examined the effect of blocking NOS on sympathetic neurotransmission in the pulmonary artery and how this is influenced by PH. Rats treated with MCT developed pulmonary hypertension. Electrical field stimulation (EFS) of the pulmonary artery produced frequency‐dependent contractions. The frequency‐response curve was shifted to the left in artery segments from pulmonary hypertensive rats. The non‐selective NOS inhibitor, L‐NAME (0.1 mM), potentiated EFS‐induced contractions at all frequencies of stimulation in both groups with no difference between the groups. 7‐NI, an inhibitor of neuronal NOS had no effect. Noradrenaline produced concentration‐dependent contractions of pulmonary artery segments from control and MCT‐treated rats. L‐NAME potentiated the contractions in control but not MCT‐treated rats. It was concluded that endothelial NO modulated adrenergic neurotransmission in the rat pulmonary artery and this was not affected by pulmonary hypertension.