| Impaired neuronal and vascular responses to angiotensin II in a rabbit congestive heart failure model. | |
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MedLine Citation:
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PMID: 14689369 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Congestive heart failure (CHF) is characterised by activation of the renin-angiotensin-aldosterone system (RAAS) and the sympathetic nervous system (SNS). Both systems are known to interact and to potentiate each other s activities. We recently demonstrated that angiotensin II (Ang II) enhances sympathetic nerve traffic via prejunctionally-located AT1-receptors. At present, little is known about the effects of Ang II at the level of the sympathetic neurones in CHF. Accordingly, we investigated the effect of Ang II in the presence and absence of the AT1-receptor antagonist, eprosartan, on stimulation-induced nerve traffic in isolated thoracic aorta preparations obtained from rabbits suffering from experimentally-induced CHF. Control-preparations were obtained from age-matched animals. Sympathetic activity was assessed by a [3H]noradrenaline spill-over model. Additionally, Ang II constrictor responses were compared between CHF and control vessels in the presence and absence of eprosartan. Additionally, to study postjunctional facilitation, the effects of Ang II on postsynaptic a-adrenoceptor-mediated responses were studied using noradrenaline. Stimulation-evoked SNS-neurotransmission was similar in both groups (CHF versus control). Ang II (0.1 nM 0.1 M) caused a concentration-dependent increase of the stimulation-evoked sympathetic outflow in both groups, with a maximum at 10 nM (control [n=7], FR2/FR1 2.03+0.11 and CHF- preparations [n=7], FR2/FR1 1.71+0.07). The enhancement by Ang II was decreased in CHF- preparations compared with controls (p<0.05). Eprosartan concentration-dependently attenuated the Ang II-enhanced (10 nM) sympathetic outflow in both CHF- and control preparations. The sympatho-inhibitory potency of eprosartan was similar in both groups (control pIC50 8.81 0.31; CHF 8.65+0.42). Ang II (1 nM 0.3 M) concentration-dependently increased the contractile force in control preparations (Emax 21.64+3.86 mN, pD2 7.63+0.02, n=7). Eprosartan (1 nM 0.1 M) influenced the Ang II- contractions via a mixed form of antagonism. In CHF-preparations, Ang II caused impaired vascular contraction. The KCl-induced contraction was decreased in the CHF- compared with control preparations (13.02+0.64 mN versus 30.40+0.89 mN). The relative Ang II contraction (% of KCl) was also decreased (2.3% vs. 58.0%). Concentration-response curves to noradrenaline (%KCl) were similar (control pD2 6.93+0.05, Emax 131.0+2.7; CHF pD2 7.00+0.05, Emax 136.7+2.6) (p>0.05) and were not affected by Ang II. We conclude that Ang II-enhanced sympathetic neurotransmission is mediated by the prejunctional AT1-receptor in both control and CHF-preparations. The decreased facilitation of SNS effects by Ang II may be explained by down-regulation or desensitisation of the neuronal AT1-receptor. Additionally, the aortic contractile capacity in heart failure rabbits appears to be decreased, probably as a result of heart failure-associated neuroendocrine and functional changes. |
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Authors:
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Alexander Nap; Charly N W Belterman; Marie-Jeanne Mathy; Jippe C Balt; Martin Pfaffendorf; Pieter A van Zwieten |
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Publication Detail:
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Type: In Vitro; Journal Article |
Journal Detail:
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Title: Journal of the renin-angiotensin-aldosterone system : JRAAS Volume: 4 ISSN: 1470-3203 ISO Abbreviation: J Renin Angiotensin Aldosterone Syst Publication Date: 2003 Dec |
Date Detail:
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Created Date: 2003-12-22 Completed Date: 2004-01-30 Revised Date: 2007-11-15 |
Medline Journal Info:
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Nlm Unique ID: 100971636 Medline TA: J Renin Angiotensin Aldosterone Syst Country: England |
Other Details:
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Languages: eng Pagination: 220-7 Citation Subset: IM |
Affiliation:
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Department of Pharmacotherapy, University of Amsterdam, Amsterdam, 1105 AZ, The Netherlands. a.nap@amc.uva.nl |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Acrylates
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administration & dosage,
pharmacology Angiotensin II / administration & dosage, pharmacology* Angiotensin II Type 1 Receptor Blockers Animals Aorta, Thoracic / drug effects*, innervation, physiopathology* Dose-Response Relationship, Drug Electric Stimulation Heart Failure / physiopathology* Imidazoles / administration & dosage, pharmacology Male Osmolar Concentration Rabbits Sympathetic Nervous System / drug effects*, physiopathology* Thiophenes* |
| Chemical | |
Reg. No./Substance:
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0/Acrylates; 0/Angiotensin II Type 1 Receptor Blockers; 0/Imidazoles; 0/Thiophenes; 11128-99-7/Angiotensin II; 133040-01-4/eprosartan |
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