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.
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.
Hu
K
K
Medizinische Universitätsklinik, Universität Würzburg, Germany.
Bahner
U
U
Gaudron
P
P
Palkovits
M
M
Ring
M
M
Fehle
A
A
Kruse
B
B
Ertl
G
G
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000097:blood*; D001921:Brain / Q000187:drug effects*; D002529:Cerebellar Nuclei / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006439:Hemodynamics / Q000187:drug effects; D007546:Isoquinolines / Q000627:therapeutic use; D019808:Losartan / Q000037:antagonists & inhibitors / Q000627:therapeutic use; D008297:Male; D008955:Models, Cardiovascular; D009203:Myocardial Infarction / Q000188:drug therapy*; D000077583:Quinapril; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000627:therapeutic use*; D044005:Tetrahydroisoquinolines; D016896:Treatment Outcome; D014655:Vascular Resistance / Q000187:drug effects; D016277:Ventricular Function, Left / Q000187:drug effects
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D007546:Isoquinolines; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D044005:Tetrahydroisoquinolines; D009320:Atrial Natriuretic Factor; D019808:Losartan; D000077583:Quinapril