Improved cardiovascular function with aminoguanidine in DOCA-salt hypertensive rats

Chan, Vincent, Hoey, Andrew and Brown, Lindsay (2006) Improved cardiovascular function with aminoguanidine in DOCA-salt hypertensive rats. British Journal of Pharmacology, 148 7: 902-908. doi:10.1038/sj.bjp.0706801


Author Chan, Vincent
Hoey, Andrew
Brown, Lindsay
Title Improved cardiovascular function with aminoguanidine in DOCA-salt hypertensive rats
Journal name British Journal of Pharmacology   Check publisher's open access policy
ISSN 0007-1188
1476-5381
Publication date 2006
Sub-type Article (original research)
DOI 10.1038/sj.bjp.0706801
Volume 148
Issue 7
Start page 902
End page 908
Total pages 7
Editor Humphrey Rang
Place of publication West Sussex, United Kingdom
Publisher John Wiley & Sons
Collection year 2006
Language eng
Subject C1
320502 Basic Pharmacology
730106 Cardiovascular system and diseases
Abstract 1 The ability of aminoguanidine (AG), an inhibitor of collagen crosslinking, to prevent changes in cardiac and vascular structure and function has been determined in the deoxycorticosterone acetate (DOCA)-salt hypertensive rat as a model of the cardiovascular remodelling observed in chronic human hypertension. 2 Uninephrectomized rats (UNX) administered DOCA (25 mg every fourth day s.c.) and 1% NaCl in drinking water for 28 days developed cardiovascular remodelling shown as systolic hypertension, left ventricular hypertrophy, increased thoracic aortic and left ventricular wall thickness, increased left ventricular inflammatory cell infiltration together with increased interstitial collagen and increased passive diastolic stiffness, impaired contractility, prolongation of the action potential duration and vascular dysfunction. 3 Treatment with AG (0.05-0.1% in drinking water; average 182 +/- 17 mg kg(-1) day(-1) in DOCA-salt rats) decreased blood pressure (DOCA-salt 176 +/- 4; + AG 144 +/- 5 mmHg; *P < 0.05 vs DOCA-salt), decreased left ventricular wet weights (DOCA-salt 3.17 +/- 0.07; + AG 2.66 +/- 0.08 mg g(-1) body wt*), reduced diastolic stiffness constant (DOCA-salt 30.1 +/- 1.2; + AG 24.3 +/- 1.2* (dimensionless)), improved cardiac contractility (DOCA-salt 1610 +/- 130; + AG 2370 +/- 100 mmHg s(-1)*) and vascular reactivity (3.4-fold increase in maximal contractile response to noradrenaline, 3.2-fold increase in maximal relaxation response to acetylcholine, twofold increase in maximal relaxation response to sodium nitroprusside) and prolonged the action potential duration at 50% repolarization without altering collagen content or inflammatory cell infiltration. 4 Thus, cardiovascular function in DOCA-salt hypertensive rats can be improved by AG independent of changes in collagen content. This suggests that collagen crosslinking is an important cause of cardiovascular dysfunction during cardiovascular remodelling in hypertension.
Keyword Aminoguanidine
Collagen crosslinking
Doca-salt rats
Hypertension
Remodelling
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

 
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Created: Wed, 15 Aug 2007, 08:49:22 EST