| The interaction between nitric oxide (NO) and endothelin (ET-1) has been a keen area of research in the past decade. Our previous studies showed that the sustained hypertensive response observed within five minutes after blocking the production of NO could be reversed using an ET A/B receptor (ETA/BR) antagonist. This finding suggested that the predominant role of NO is not just as a chronic vasodilator but rather also as a local negative modulator of ET vasoconstrictor activity. Despite this suggestion, no significant changes in ET-1 have been found in vascular tissues obtained from rats immediately following experimental NO deficiency. As a result of these findings, it may be that the regulation of “free” versus “total” levels of ET is more relevant.; To further elucidate the mechanism underlying this “five minute' mystery”, in vitro studies were performed to study ET-1 binding in rat and bovine aortic endothelial cells. ET-1 binding proteins unrelated to ETA/BR were found in both species, implying their possible physiological role as ET-1 storage sites. However, binding experiments performed in the presence of NO did not result in altered ET-1 binding to those sites. Similarly, in cultured calf pulmonary aortic endothelial cells, exposure to blockers of NO synthesis did not result in a change in ET-1 release or intercellular storage, suggesting that NO might not affect the amount of endothelial “free” ET-1 as hypothesized.; It may be, however, that the in vitro conditions deviated substantially from the in vivo environment such that the results observed may actually be due to the experimentally altered microenvironment. Thus, a complete understanding of the mechanisms of acute hypertension following NO blockage will have to await further experimentation. |
