Endothelins are a family of 21-amino acid peptides synthesized by endothelial cells and some tumors (67,68). Endothelins are potent regulators of vascular tones (69). In addition, mitogenic activity of endothelin on vascular smooth muscle and stromal fibroblasts have been demonstrated (68,70,71). Short term fasting or chronic dietary restriction in rats has been found to decrease plasma endothelin levels (72), in contrast to many other types of pathophysiologic stressors previously shown to increase plasma endothelin level (73-77). Perhaps altered endothelin expression may participate in homeostatic adjustments related to the need for overall host energy conservation during chronic restriction. How endothelin may modulate tumor vascularity and blood flow under conditions of dietary restriction remains to be explored.

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