Venous contraction to endothelin-1 in congestive heart failure

Endothelin-1 (ET-1) is produced by endothelial cells and can stimulate either the ET_A or the ET_B receptors. The role of ET-1 and the identity of the endothelin receptors involved in mediating tone in the mesenteric small veins of the Golden Syrian hamster are not known. ET-1 induces venoconstriction, thereby increasing the preload to the heart in congestive heart failure. However, mechanisms mediating contraction to ET-1 in the mesenteric small veins of the cardiomyopathic hamsters in the early and late stages of CHF are not known. Therefore, mechanisms mediating ET-1 induced contraction were determined in the mesenteric small veins of the Golden Syrian and cardiomyopathic hamsters in the early and late stages of CHF.; Baseline intraluminal diameter of small veins was measured before and after treatment with either ET_A or ET_B receptor antagonists. ET-1 induced contraction was higher in the early stage of CHF, while it was decreased in the late stage of CHF. Blockade of the ET_A receptor decreased ET-1 induced contraction in the mesenteric small veins from the control and cardiomyopathic hamsters in both the early and late stage of CHF. ET_B receptor blockade decreased the ET-1 induced contraction in the control and cardiomyopathic hamsters in the early, but not late, stage of CHF. Therefore, ET-1 induced contraction in the mesenteric small veins is mediated by the ET_A receptors alone in the late stage of CHF, while both the ET_A and ET_B receptors mediate vasoconstriction in the controls and in the early stage of CHF.; Stimulation of ET-1 receptors is associated with an increase in calcium levels within the vascular smooth muscle cells.{09}Following ET-1, calcium levels within the vascular smooth muscle cell were increased to a larger extent in the early stage of CHF, than in the late stage of CHF, in agreement with the vascular reactivity data. Calcium levels were also measured before and after treatment with either ET_A or ET_B receptor antagonists. Blockade of the ET_A receptor inhibited the ET-1 induced increase in calcium levels in the mesenteric small veins from the control and cardiomyopathic hamsters in both the early and late stage of CHF. However, ET_B receptor blockade inhibited the ET-1 induced increase in calcium levels in only the control and cardiomyopathic hamsters in the early stage of CHF. These results indicate the absence of a functional responses mediated by the ET _B receptor in the late stage of CHF.; Studies have shown that NO can modulate the contraction to ET-1 in the vasculature. Baseline intraluminal diameter of small veins were measured before and after treatment with N-nitro-L-arginine (LNA), a specific inhibitor of nitric oxide synthase. LNA decreased the contraction to ET-1 in the early stage of CHF, but increased contraction to ET-1 in the late stage of CHF. This indicates that NOS mediates a vasodilatory effect that counteracts contraction to ET-1 in the late stage, but contributes to the vasoconstrictor effect of ET-1 in the late stage of CHF. (Abstract shortened by UMI.)...