Chronic effects of ACE-inhibition (quinapril) and angiotensin-II type-1 receptor blockade (losartan) on atrial natriuretic peptide in brain nuclei of rats with experimental myocardial infarction |
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Authors: | Kai Hu Udo Bahner Peter Gaudron Miklos Palkovits Markus Ring Andrea Fehle Bernhard Kruse Georg Ertl |
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Institution: | Medizinische Universit?tsklinik, Universit?t Würzburg, Josef-Schneider-Stra?e 2, 98080 Würzburg, Germany, DE Universit?tsklinik Mannheim/Heidelberg, 68167 Mannheim, Germany, DE Department of Anatomy, Semmelweis University, Medical School, 1094 Budapest, Hungary, HU
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Abstract: | Alterations of the central nervous system may be important for imbalance of cardiovascular and fluid regulation in heart
failure. The central renin-angiotensin and atrial natriuretic peptide (ANP) systems act as mutual antagonists. The effects
of angiotensin converting enzyme (ACE) inhibition (quinapril, 6 mg/kg/day) and angiotensin II type 1 (AT1) receptor blockade (losartan, 10 mg/kg/day) on ANP levels in 18 selected, microdissected brain nuclei were determined in
sham-operated rats and rats with left ventricular dysfunction 8 weeks after myocardial infarction (MI). Plasma ANP tended
to increase in MI rats and was further increased by quinapril. ANP was decreased in 12 brain areas of MI rats. ANP concentration
was also significantly decreased by quinapril in six brain nuclei including subfornical organ and organum vasculosum laminae
terminalis (areas lacking blood-brain barrier), and by losartan in 16 brain nuclei outside and within the blood-brain barrier
in sham operated rats. However, both quinapril and losartan prevented a further reduction of central ANP as a result of myocardial
infarction. These data suggest that there are effects on central ANP that result from chronic left ventricular dysfunction
as well as an ACE-inhibitor and AT1-antagonist. Mechanisms and consequences of central ANP depression remain unclear. They could, however, support systemic vasoconstriction
and sodium and fluid retention.
Received: 8 October 1999, Returned for 1. revision: 28 December 1999, 1. Revision received: 2 March 2000, Returned for 2.
revision: 17 April 2000, 2. Revision received: 20 October 2000, Accepted: 9 November 2000 |
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Keywords: | Angiotensin converting enzyme inhibition – Ang II – blood-brain barrier – ANP |
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