Endothelin-1 and blood pressure after inhibition of nitric oxide synthesis in human septic shock.

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Abstract
Background —The systemic hypotension during human sepsis has been ascribed to increased production of nitric oxide (NO). Therefore, inhibitors of NO synthesis have been used in the treatment of hypotension in patients with septic shock. In addition, NO production may inhibit the synthesis and vasoconstrictor effects of endothelin-1 (ET-1). In this study, we tested whether ET-1 contributed to the vasopressor action of the NO synthase inhibitor N G -nitro- l -arginine methyl ester (L-NAME) in patients with severe septic shock. Methods and Results —Compared with healthy volunteers, patients with septic shock had increased plasma levels of nitrite/nitrate (37±5 [SEM] versus 12±5 mmol/L, P P −1 · h −1 IV) for 12 hours increased mean arterial pressure by 43±5% and systemic vascular resistance by 64±10% (both P P Conclusions —NO and ET-1 may both play a role in the cardiovascular derangements of human sepsis. Although L-NAME does not increase ET-1 concentration in patients with septic shock, the vasopressor response induced by L-NAME depends on the plasma level of ET-1. These findings may indicate that inhibitors of NO synthesis unmask a tonic pressor response of ET-1 in human septic shock.