ACE inhibition reduces infarction in normotensive but not hypertensive rats: correlation with cortical ACE activity.
Angiotensin-converting enzyme (ACE) inhibition can reduce stroke risk by up to 43% in humans and reduce the associated disability, and hence understanding the mechanism of improvement is important. In animals and humans, these effects may be independent of the blood pressure-lowering effects of ACE inhibition. Normotensive (Wistar-Kyoto (WKY)) and hypertensive (spontaneously hypertensive rat (SHR)) animals were treated with the ACE inhibitors ramipril or lisinopril for 7 or 42 days before 2 hours of transient middle cerebral artery occlusion (MCAo). Blood pressure, serum ACE, and blood glucose levels were measured and stroke infarct volume was recorded 24 hours after stroke. Despite greater reductions in blood pressure, infarct size was not improved by ACE inhibition in hypertensive animals. Short-term ACE inhibition produced only a modest reduction in blood pressure, but WKY rats showed marked reductions in infarct volume. Long-term ACE inhibition had additional reductions in blood pressure; however, infarct volumes in WKY rats did not improve further but worsened. WKY rats differed from SHR in having marked cortical ACE activity that was highly sensitive to ACE inhibition. The beneficial effects of ACE inhibition on infarct volume in normotensive rats do not correlate with changes in blood pressure. However, WKY rats have ACE inhibitor-sensitive cortical ACE activity that is lacking in the SHR.
Porritt
Michelle J
MJ
Department of Medicine, University of Melbourne, Austin Health, Heidelberg, Victoria, Australia.
Chen
Michelle
M
Rewell
Sarah S J
SS
Dean
Rachael G
RG
Burrell
Louise M
LM
Howells
David W
DW
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology; D006973:Hypertension / Q000188:drug therapy* / Q000201:enzymology; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy* / Q000201:enzymology; D017706:Lisinopril / Q000627:therapeutic use*; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D017257:Ramipril / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar
D000806:Angiotensin-Converting Enzyme Inhibitors; D017706:Lisinopril; D007703:Peptidyl-Dipeptidase A; D017257:Ramipril
Nihon Yakurigaku Zasshi. 1998 Oct;112 Suppl 1:53P-57P
10190134
Exp Toxicol Pathol. 2006 Jan;57(3):213-9
16343876
Am J Physiol Regul Integr Comp Physiol. 2007 May;292(5):R1881-92
17234953
J Neurosci Methods. 2006 Sep 15;155(2):285-90
16513179
J Hypertens. 1990 Aug;8(8):733-40
2170513
Drugs Exp Clin Res. 1995;21(2):41-9
7555608
Clin Exp Hypertens. 1996 Feb;18(2):201-26
8869001
Lancet Neurol. 2007 Mar;6(3):215-22
17303527
N Engl J Med. 2000 Jan 20;342(3):145-53
10639539
Clin Exp Hypertens. 1997 Oct;19(7):1079-99
9310205
Stroke. 1989 Jan;20(1):84-91
2643202
J Cardiovasc Pharmacol. 1995 Sep;26(3):426-36
8583785
Hypertension. 2001 May;37(5):1336-40
11358950
J Renin Angiotensin Aldosterone Syst. 2000 Mar;1(1):18-20
11967789
Hypertension. 1988 Mar;11(3):230-8
2832327
Curr Drug Targets Cardiovasc Haematol Disord. 2005 Apr;5(2):127-34
15853754
N Engl J Med. 2006 Aug 10;355(6):549-59
16899775
Hypertension. 1995 Nov;26(5):828-34
7591025
Am J Cardiol. 2002 Jan 24;89(2A):18A-25A; discussion 25A-26A
11835907
Hypertension. 1993 Aug;22(2):139-46
8340149
Stroke. 2001 Aug;32(8):1732-8
11486098
Exp Anim. 2004 Jan;53(1):67-72
14993746
Br J Clin Pharmacol. 1989;28 Suppl 2:115S-130S; discussion 130S-131S
2557876
Lancet. 1994 Nov 19;344(8934):1383-9
7968073
Clin Neurol Neurosurg. 2006 Oct;108(7):638-43
16300876
Stroke. 2003 Oct;34(10):2333-8
12958329
Lancet. 1997 May 17;349(9063):1436-42
9164317
Health Policy. 2007 Oct;83(2-3):287-94
17368861
Lancet. 2001 Dec 22-29;358(9299):2130-1
11784631
Aust Fam Physician. 2007 Nov;36(11):892-5
18043773
Peptides. 1993 Sep-Oct;14(5):883-91
8284265
Brain Res. 1988 Mar 15;444(1):46-52
2896061
Hypertension. 1995 May;25(5):928-34
7737729
Scand J Clin Lab Invest. 1987 Jun;47(4):411-4
3037682
Neuroreport. 2005 Nov 28;16(17):1963-7
16272888
J Cardiovasc Pharmacol. 1991 Oct;18(4):478-86
1724523
Am J Hypertens. 1991 Aug;4(8):680-7
1930850
Am J Physiol. 1994 Nov;267(5 Pt 1):E745-53
7977726
J Clin Epidemiol. 2003 May;56(5):479-86
12812823
Jpn Circ J. 1981 Sep;45(9):1111-5
6271998
Stroke. 2002 Sep;33(9):2297-303
12215602
J Hypertens. 2008 Mar;26(3):544-52
18300867
Eur J Pharmacol. 1999 May 28;373(1):21-33
10408248
Circulation. 1999 Jan 19;99(2):216-23
9892586
Clin Exp Pharmacol Physiol. 1980 Sep-Oct;7(5):551-4
6256105
N Engl J Med. 2008 Sep 25;359(13):1317-29
18815396