title: An inhibitor of inducible nitric oxide synthase decreases forearm blood flow in patients with congestive heart failure.
abstract: OBJECTIVE
  The functional activation of inducible nitric oxide synthase (iNOS) was evaluated as a source of nitric oxide (NO) in the forearm of patients with heart failure.
  
  
  BACKGROUND
  Although endogenous NO is normally produced by constitutive NO synthase (cNOS) in patients with congestive heart failure (CHF), expression of iNOS provides an additional source of NO. However, there are no in vivo studies showing functional activation of iNOS in humans.
  
  
  METHODS
  A nonselective NOS inhibitor, N(G)-monomethyl-L-arginine (L-NMMA), and a selective inhibitor of iNOS, aminoguanidine, were administered intra-arterially in graded doses into the brachial arteries of 13 patients with CHF and 10 normal control subjects. Forearm blood flow (FBF) was measured simultaneously in the infused and noninfused arms by plethysmography. Arterial and venous plasma concentrations of nitrite/nitrate (NOx) were measured at baseline and at the highest dose of each drug.
  
  
  RESULTS
  L-NMMA significantly reduced the FBF ratio between the infused and noninfused arms in both the control and patient groups (35 +/- 12% and 34 +/- 10%, respectively; both p < 0.001). Aminoguanidine at the same concentration significantly reduced the ratio in the patient group (15 +/- 9%, p < 0.01), with no change in the control group. The arterial NOx concentration was not affected by either drug; however, venous NOx concentrations were significantly decreased in both the control and patient groups by L-NMMA (18 +/- 5% and 18 +/- 17%, respectively; both p < 0.05) and in the patient group only by aminoguanidine (7 +/- 6%, p < 0.05).
  
  
  CONCLUSIONS
  These findings suggest that NO production in the forearms of patients with CHF is induced partly by iNOS activation, whereas in normal subjects, it can be ascribed to cNOS activation.
authors.affiliation: Fourth Department of Internal Medicine, Izumo, Japan. yuyu@shimane-med.ac.jp
authors.forename: Y
authors.initials: Y
authors.lastname: Ishibashi
authors.forename: T
authors.initials: T
authors.lastname: Shimada
authors.forename: Y
authors.initials: Y
authors.lastname: Murakami
authors.forename: N
authors.initials: N
authors.lastname: Takahashi
authors.forename: T
authors.initials: T
authors.lastname: Sakane
authors.forename: T
authors.initials: T
authors.lastname: Sugamori
authors.forename: S
authors.initials: S
authors.lastname: Ohata
authors.forename: S
authors.initials: S
authors.lastname: Inoue
authors.forename: Y
authors.initials: Y
authors.lastname: Ohta
authors.forename: K
authors.initials: K
authors.lastname: Nakamura
authors.forename: H
authors.initials: H
authors.lastname: Shimizu
authors.forename: H
authors.initials: H
authors.lastname: Katoh
authors.forename: M
authors.initials: M
authors.lastname: Hashimoto
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D009320:Atrial Natriuretic Factor / Q000097:blood / Q000187:drug effects; D001783:Blood Flow Velocity / Q000187:drug effects*; D016022:Case-Control Studies; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000201:enzymology; D005260:Female; D005542:Forearm / Q000098:blood supply*; D006146:Guanidines / Q000494:pharmacology*; D006333:Heart Failure / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D010991:Plethysmography; D012720:Severity of Illness Index; D013997:Time Factors; D014664:Vasodilation / Q000187:drug effects*; D019323:omega-N-Methylarginine / Q000494:pharmacology*
chemical_list: D006146:Guanidines; D020097:Natriuretic Peptide, Brain; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D009320:Atrial Natriuretic Factor; D019001:Nitric Oxide Synthase; D000109:Acetylcholine; C004479:pimagedine