Enhanced basal nitric oxide production in heart failure: another failed counter-regulatory vasodilator mechanism?
Endothelial dysfunction in heart failure could impair nitric oxide production and lead to increased vascular resistance. If endogenous production of nitric oxide is reduced, NG-monomethyl-L-arginine (L-NMMA), an inhibitor of such production, should have a diminished vasoconstrictor effect. We administered L-NMMA to 12 patients being investigated for heart failure. L-NMMA increased median pulmonary and systemic vascular resistances by 61 (range -3 to 240) and 430 (63 to 1609) dynes s cm-5, respectively (p < 0.03 and p < 0.005). Arterial pressures also increased. Median cardiac output fell by 0.6 (0 to -2.3) L per min (p < 0.005). These data suggest that vascular nitric oxide may be another example of a failed counter-regulatory vasodilator system in heart failure.
Habib
F
F
Department of Medicine (Cardiology), Royal Postgraduate Medical School, Hammersmith Hospital, London, UK.
Dutka
D
D
Crossman
D
D
Oakley
C M
CM
Cleland
J G
JG
D000368:Aged; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D002303:Cardiac Output, Low / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000378:metabolism; D006334:Heart Function Tests; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000494:pharmacology / Q000502:physiology / Q000627:therapeutic use*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology; D019323:omega-N-Methylarginine
D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine