title: Nitric oxide and potassium channels are involved in brain natriuretic peptide induced vasodilatation in man.
abstract: OBJECTIVE
  Brain natriuretic peptide (BNP) causes vasodilatation but the mechanisms by which this is accomplished are not fully known. The aim of the present study was to determine whether, besides K+Ca2+-channels, nitric oxide (NO) is involved in BNP-induced vasodilatation.
  
  
  METHODS
  We studied 10 healthy males twice, in random order, at an interval of 2 weeks. Experiments always started with infusion of BNP (8-16-32-64 pmol/dl per min) into the brachial artery. On the first day this infusion was followed by a second BNP infusion combined with the K+Ca2+-channel-blocker, tetraethylammonium (TEA, 0.1 mg/dl per min), and on the other day by BNP infusion combined with the NO-synthase inhibitor, l-NG-monomethyl arginine (l-NMMA, 0.8 mumol/dl per min). The latter was then followed by a combined infusion of BNP, l-NMMA and TEA. All infusions were separated by a 1 h washout period. Forearm blood flow (FBF) was determined by venous occlusion plethysmography.
  
  
  RESULTS
  Mean arterial pressure and heart rate did not change during any of the experiments. BNP alone induced a dose-dependent dilatation, which was similar on both days. TEA, l-NMMA, and their combination all reduced the BNP-induced dilatation (P < 0.05). The combined infusion had a significantly greater effect than TEA alone (P = 0.005). BNP infusions were associated with a significant increase in plasma cyclic guanosine monophosphate (cGMP) and C-type natriuretic peptide (CNP) (P < 0.05).
  
  
  CONCLUSIONS
  BNP induces arterial vasodilatation not only by opening K+Ca2+-channels, but also via stimulation of NO production. In addition, BNP stimulates net CNP increase.
authors.affiliation: Department of Medicine, Cardiovascular Research Institute Maastricht, Maastricht, The Netherlands.
authors.forename: Kim
authors.initials: K
authors.lastname: van der Zander
authors.forename: Alphons J H M
authors.initials: AJ
authors.lastname: Houben
authors.forename: Abraham A
authors.initials: AA
authors.lastname: Kroon
authors.forename: Jo G R
authors.initials: JG
authors.lastname: De Mey
authors.forename: Paul A B M
authors.initials: PA
authors.lastname: Smits
authors.forename: Peter W
authors.initials: PW
authors.lastname: de Leeuw
mesh_terms: D000328:Adult; D006152:Cyclic GMP / Q000097:blood; D004338:Drug Combinations; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005542:Forearm / Q000098:blood supply; D006801:Humans; D008297:Male; D020097:Natriuretic Peptide, Brain / Q000494:pharmacology*; D020098:Natriuretic Peptide, C-Type / Q000097:blood; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000502:physiology*; D012039:Regional Blood Flow / Q000187:drug effects; D019789:Tetraethylammonium / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology*; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: D004338:Drug Combinations; D004791:Enzyme Inhibitors; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D014665:Vasodilator Agents; D020097:Natriuretic Peptide, Brain; D020098:Natriuretic Peptide, C-Type; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D019789:Tetraethylammonium; D006152:Cyclic GMP