Antagonism of LTD4-evoked relaxation in canine renal artery and vein

Abstract

The goal of this study was to characterize further the manner in which the peptide leukotriene (LT) D4 evokes endothelium-dependent relaxation of the canine renal vein (RV) and artery (RA). The effects of four chemically and structurally dissimilar LT receptor antagonists and pertussis toxin (PTX), on LTD4-evoked relaxation of RV and RA rings, were determined and compared. In the presence of ICI 198,615 (10(-5) M), relaxation of both the RA and RV evoked by LTD4 was markedly attenuated. MK-571 (10(-5) M) altered neither RA nor RV relaxation evoked by LTD4. Relaxation of the RV but not the RA, evoked by LTD4, was attenuated in the presence of LY171,883 (10(-5) M). L649,923 (10(-5) M) solely inhibited LTD4-evoked relaxation of the RA. Pretreatment of vascular rings with PTX (250 ng/ml) for 2 h attenuated the vasomotor relaxation evoked by LTD4 in the RA but not in the RV. These observations suggest that LTD4-evoked relaxation of the RA and RV is dependent on different mechanisms. The endothelium-dependent response produced in the RA apparently involves a PTX-sensitive G protein. It is proposed that multiple signal transduction pathways and perhaps different LTD4 receptors may account for the diverse activity of LTD4.