We have investigated the effect of elevated n-3 (omega-3) fatty acid content in the diet on arrhythmias, ischemic damage, and inflammatory cell infiltration into the reperfused left ventricular free wall (LVFW). Weanling rats were fed purified diets in which the lipid was replaced with either corn oil (CO) or menhaden oil (MO). After 4 wk, MO feeding resulted in significant elevations in both the ratio of n-3 to n-6 fatty acids and the unsaturation index in myocardial phospholipids. Rats were subjected to 15 min of ischemia followed by reperfusion. After 6 h of reperfusion of the left coronary artery there was significantly less creatine kinase (CK) lost from the LVFW of rats fed MO. Leukocyte infiltration into the LVFW, as measured by myeloperoxidase (MPO) activity, was also significantly reduced with MO feeding at 6 h. Arrhythmias were studied in a separate group of 17 rats; both the incidence and severity of ventricular tachycardia and ventricular fibrillation were significantly reduced during the ischemic and reperfusion periods with MO feeding. After 24 h of reperfusion there was also significantly less CK lost from the LVFW of MO-fed rats; however, there was no significant difference in tissue MPO activity in ventricular homogenates. Survival after 24 h of reperfusion was 76% (16/21) for MO- and 41% (9/22) for CO-fed rats. The data suggest a protective effect for dietary MO in myocardial ischemia-reperfusion, which may involve both an early reduction in leukocyte infiltration and a reduction in the incidence of fatal arrhythmias.

LY-171883 has a protective effect in ischaemia-reperfusion injury to the myocardium. These findings suggest a role for peptide leukotrienes both in the extension of ischaemic damage and in post-ischaemic ventricular dysfunction during reperfusion.

We have previously shown that progesterone increased sulfate uptake in glandular epithelial cells of guinea pig endometrium. To investigate whether cAMP might be the cause of the progesterone effect on sulfate uptake, cAMP accumulation and the effect of cAMP on sulfate uptake were evaluated in cells treated with 17 beta-estradiol alone or with progesterone. Progesterone provoked an increase in the intracellular cAMP accumulation in cells treated with 17 beta-estradiol. Moreover, cAMP or forskolin elicited the same marked increase in sulfate uptake as that observed with progesterone. The effect of progesterone on sulfate uptake was abolished by blocking either the cAMP pathway or the genomic action of progesterone and was independent of the cAMP-activatable apical chloride channel. This study is the first evidence of cAMP activation of sulfate uptake and suggests a genomic effect of progesterone on the production of cAMP which activates the sulfate transport system in a short term activation and a long term activation independent of transcriptional or translational events. The endometrium is a unique tissue that undergoes profound highly regulated modifications during the secretory phase in providing a suitable environment for embryo implantation. The regulation of sulfate uptake could participate in this process.

The present findings support a role for thromboxane A2 and peptide leukotrienes D4/E4 as important mediators in circulatory shock and suggest that combined thromboxane/leukotriene receptor antagonism may have superior therapeutic efficacy to leukotriene receptor antagonism.

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