Effects of nitric oxide-modulating amino acids on coronary vessels: relevance to sepsis

Excessive nitric oxide (NO) production in septic shock is thought to contri bute to the associated profound hypotension. Here we show that despite indu ction of NO synthase (NOS) in the hearts of endotoxin-treated rats, coronar y vascular responses to the contractile peptide endothelin-1, were not modi fied. This was not due to any change in the expression of endothelin recept ors. However, when the substrate for NOS, L-arginine, was added to the perf usate, increases in coronary perfusion pressure stimulated by endothelin we re reduced in hearts from endotoxin-treated animals compared to those from controls, in addition, L-glutamine, which blocks the generation of L-argini ne from intracellular stores, enhanced the increase in perfusion pressure s timulated by endothelin-1. These data suggest that L-arginine becomes rate limiting for the production of NO in the coronary vessels during septic sho ck. Moreover, it suggests that vascular reactivity may be modulated positiv ely or negatively by supplementation with the relevant amino acids. (C) 200 0 Elsevier Science B.V. All rights reserved.