Nitric oxide and potassium channels are involved in brain natriuretic peptide induced vasodilatation in man.
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.
van der Zander
Kim
K
Department of Medicine, Cardiovascular Research Institute Maastricht, Maastricht, The Netherlands.
Houben
Alphons J H M
AJ
Kroon
Abraham A
AA
De Mey
Jo G R
JG
Smits
Paul A B M
PA
de Leeuw
Peter W
PW
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
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