Publications (2)4.37 Total impact
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Article: Impairment by lovastatin of neural relaxation of the rabbit sphincter of Oddi
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ABSTRACT: We sought whether inhibition of cholesterol biosynthesis by lovastatin influenced the nitrergic relaxation response of the sphincter of Oddi. Rabbit sphincters of Oddi rings were tested for changes in isometric tension in response to field stimulation in the presence of 4 μM guanethidine and 1 μM atropine. Tissue samples were then analyzed for cAMP and cGMP content by radioimmunoassay for nitric oxide concentration by electron spin resonance and for vasoactive intestinal peptide and calcitonin gene-related peptide (CGRP) release by radioimmunoassay. Membrane Gsα protein was determined by Western blot analysis. Field stimulation relaxed the preparations with an increase in nitric oxide, cAMP and cGMP concentrations at increased calcitonin gene-related peptide and vasoactive intestinal polypeptide (VIP) release. Preparations from rabbits pre-treated with lovastatin (5 mg/kg/day intragastrically, over 5 days) contracted under the same conditions with an attenuated cGMP-increase at preserved increase in NO content and neuropeptide release. The relaxation was recaptured combining lovastatin with farnesol (1 mg/kg intravenously, twice a day for 5 days). The field stimulation-induced increase in cyclic nucleotides was also restored. Lovastatin decreased membrane Gsα protein content, which was re-normalized by farnesol. Farnesol treatment reinstates neurogenic relaxation of the sphincter of Oddi deteriorated by lovastatin possibly by normalizing G-protein coupling.European Journal of Pharmacology 12/2001; · 2.52 Impact Factor -
Article: ROLE OF NITRIC OXIDE AND TPEN, A POTENT METAL CHELATOR, IN ISCHAEMIC AND REPERFUSED RAT ISOLATED HEARTS
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ABSTRACT: SUMMARY1. The role of nitric oxide (NO) was studied in the control of ischaemic/reperfused cardiac function and the effect of N, N, N', N'-tetrakis-[2-pyridylmethyl]-ethylenediamine(TPEN), a potent metal chelator, on the regulation of cardiac NO formation.2. Rat isolated working hearts were subjected to 30 min is-chaemia and reperfusion. The incidence of reperfusion-induced ventricular fibrillation (VF), ventricular tachycardia (VT) and the recovery of cardiac function were measured. Nitric oxide was detected by electron spin resonance (ESR) spectroscopy.3. With 5.0, 7.5 and 10.0 μmol/L of TPEN administered prior to ischaemia, the drug produced a reduction in the incidence of VF from its control value of 100% to 25% (P<0.05), 17% (P<0.05) and 8% (P<0.05), respectively. The incidence of VT followed the same pattern.4. When TPEN was given at the moment of reperfusion, a reduction in the incidence of VF and VT was still observed. Reduction in the incidence of VF and VT was reflected in the improvement of cardiac function both in the pre- and post-ischaemic TPEN-treated groups.5. TPEN reduced basal cardiac NO content and prevented the accumulation of NO during ischaemia/reperfusion.6. The results show that TPEN exerts beneficial effects on postischaemic cardiac function and dysrhythmias in relation to inhibition of the accumulation of NO in ischaemic/reperfused myocardium.Clinical and Experimental Pharmacology and Physiology 07/1998; 25(7‐8):496 - 502. · 1.85 Impact Factor
