The influence of phosphodiesterase inhibitor, rolipram, on hemodynamics inlipopolysaccharide-treated rats

Administration of bacterial endotoxin (lipopolysaccharide, LPS) intravenous ly has been noted to produce a shock state, which is characterized by hypot ension and mutli-organ system failure. The aim of the present investigation was to (a) examine the influence of rolipram on hemodynamics, plasma level s of tumor necrosis factor-alpha (TNF-alpha) levels, and production of indu cible nitric oxide synthase (iNOS) in the lungs, ex vivo, in LPS-treated ra ts, and (b) determine the cardiovascular effects of a selective alpha (1)-a drenoceptor agonist, methoxamine, in the absence or presence of rolipram in rats treated with LPS. Blood pressure, cardiac index, heart rate and arter ial resistance were assessed in Long-Evens rats anesthetized with thiobutab arbital. Administration of LPS to animals resulted in a significant reducti on in cardiac index over time. The administration of LPS to rats resulted i n a substantial rise in the plasma levels of TNF-alpha. Furthermore, the in jection of LPS resulted in a significant increase in the iNOS activity in t he lungs. Pre-treatment with rolipram prevented the decline in cardiac inde x in animals that received LPS. Infusion of methoxamine into animals inject ed with rolipram and pre-treated with LPS did not result in significant cha nges in cardiac index. Pre-treatment with rolipram or dexamethasone in anim als injected with LPS significantly prevented the rise in TNF-alpha when co mpared to the respective values in vehicle-treated animals. Our present obs ervations support the view that the cardiac index can be maintained in anim als treated with LPS independent of iNOS inhibition.