Factors affecting endothelin-induced venous tone in conscious rats

There may be a relation between altered venous function, endothelin (ET)-1, and an impairment in the activity of endothelial-derived nitric oxide (NO) and prostanoids in salt-dependent hypertension. The present study examined the effects of salt intake on ET-induced changes in venomotor tone and the effects of blockade of NO synthase with N(G)-nitro-L-arginine methyl ester (L-NAME) and of cyclooxygenase with indomethacin on venomotor tone caused by the ET(B) selective agonist sarafotoxin 6c (S6c) in awake rats. Rats were anesthetized for permanent placement of catheters for measurements of arterial and venous pressures. A silicone balloon catheter was also fixed in the right atrium to produce brief circulatory arrest. Venomotor tone was estimated from measurements of mean circulatory filling pressure (MCFP) in conscious rats. There were no differences in mean arterial pressure, heart rate, or MCFP responses to short-term administration of ET-1 or S6c at different levels of salt intake. L-NAME or indomethacin did not change MCFP or the response of MCFP to short-term injection of S6c. In conclusion, neither basal MCFP nor integrated venomotor responses to short-term injection of ET-1 or S6c were altered by short-term changes in salt intake, blockade of NO synthase or cyclooxygenase. These data do not support the hypothesis that increased salt intake alters reactivity of veins to ET-1, NO, or prostanoids.