Effects of nitric oxide-modulating amino acids on coronary vessels: relevance to sepsis.
Excessive nitric oxide (NO) production in septic shock is thought to contribute to the associated profound hypotension. Here we show that despite induction of NO synthase (NOS) in the hearts of endotoxin-treated rats, coronary vascular responses to the contractile peptide endothelin-1, were not modified. This was not due to any change in the expression of endothelin receptors. However, when the substrate for NOS, L-arginine, was added to the perfusate, increases in coronary perfusion pressure stimulated by endothelin were reduced in hearts from endotoxin-treated animals compared to those from controls. In addition, L-glutamine, which blocks the generation of L-arginine from intracellular stores, enhanced the increase in perfusion pressure stimulated by endothelin-1. These data suggest that L-arginine becomes rate limiting for the production of NO in the coronary vessels during septic shock. Moreover, it suggests that vascular reactivity may be modulated positively or negatively by supplementation with the relevant amino acids.
Mitchell
J A
JA
Unit of Critical Care Medicine, Imperial College School of Medicine, Royal Brompton Hospital, Sydney Street, London, UK. j.a.mitchell@ic.ac.uk
Gray
P
P
Anning
P D
PD
Woods
M
M
Warner
T D
TD
Evans
T W
TW
D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D003331:Coronary Vessels / Q000378:metabolism*; D019332:Endothelin-1 / Q000494:pharmacology; D004731:Endotoxins / Q000633:toxicity; D004790:Enzyme Induction; D005973:Glutamine / Q000494:pharmacology*; D008297:Male; D009206:Myocardium / Q000201:enzymology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D012772:Shock, Septic / Q000378:metabolism*
D019332:Endothelin-1; D004731:Endotoxins; D012333:RNA, Messenger; D005973:Glutamine; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D019331:NG-Nitroarginine Methyl Ester