title: Brain natriuretic peptide is a potent vasodilator in aged human microcirculation and shows a blunted response in heart failure patients.
abstract: BACKGROUND
  Brain natriuretic peptide (BNP) is normally present in low levels in the circulation, but it is elevated in parallel with the degree of congestion in heart failure subjects (CHF). BNP has natriuretic effects and is a potent vasodilator. It is suggested that BNP could be a therapeutic alternative in CHF. However, we postulated that the high levels of circulating BNP in CHF may downregulate the response of microvascular natriuretic receptors. This was tested by comparing 15 CHF patients (BNP > 3000 ng/L) with 10 matched, healthy controls.
  
  
  METHODS
  Cutaneous microvascular blood flow in the forearm was measured by laser Doppler Flowmetry. Local heating (+44°C, 10 min) was used to evoke a maximum local dilator response.
  
  
  RESULTS
  Non-invasive iontophoretic administration of either BNP or acetylcholine (ACh), a known endothelium-dependent dilator, elicited an increase in local flow. The nitric oxide synthase inhibitor, l-N-Arginine- methyl-ester (L-NAME), blocked the BNP response (in controls). Interestingly, responses to BNP in CHF patients were reduced to about one third of those seen in healthy controls (increase in flow: 251% in CHF vs. 908% in controls; P < 0.001). In contrast, the vasodilator responses to ACh and to local heating were only somewhat attenuated in CHF patients. Thus, dilator capacity and nitric oxide signalling were not affected to the same extent as BNP-mediated dilation, indicating a specific downregulation of the latter response.
  
  
  CONCLUSIONS
  The findings show for the first time that microvascular responses to BNP are markedly reduced in CHF patients. This is consistent with the hypothesis of BNP receptor function is downregulated in CHF.
authors.affiliation: Department of Emergency and Internal Medicine, Institute of Clinical Sciences Lund University, Lund University Hospital, SE- 221 85 Lund, Sweden.
authors.forename: Marie-Louise
authors.initials: ML
authors.lastname: Edvinsson
authors.affiliation: Department of Emergency and Internal Medicine, Institute of Clinical Sciences Lund University, Lund University Hospital, SE- 221 85 Lund, Sweden.
authors.forename: Erik
authors.initials: E
authors.lastname: Uddman
authors.affiliation: Department of Emergency and Internal Medicine, Institute of Clinical Sciences Lund University, Lund University Hospital, SE- 221 85 Lund, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Edvinsson
authors.affiliation: Department of Emergency and Internal Medicine, Institute of Clinical Sciences Lund University, Lund University Hospital, SE- 221 85 Lund, Sweden.
authors.forename: Sven E
authors.initials: SE
authors.lastname: Andersson
keywords: Acetylcholine, Brain natriuretic peptide; Cutaneous microcirculation; Endothelial responses; Heart failure; Nitric oxide
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