Gene expression of endothelin-1 and endothelial-type nitric oxide synthase in cardiovascular tissues of stroke-prone spontaneously hypertensive rats/Izm: effects of the angiotensin-converting enzyme inhibitor aracepril.
We studied target organ-protective effects of aracepril, an angiotensin-converting enzyme inhibitor, and the expression of endothelin-1 (ET-1) and nitric oxide synthase (NOS) mRNA. Aracepril (30 mg/kg) was administered orally to Izumo strain of stroke-prone spontaneously hypertensive rats (SHR-SP/Izm) for 8 weeks from 4 weeks of age and for 4 weeks from 8 weeks of age. The expression of ET-1 and endothelial NOS (eNOS) mRNA in the heart, aorta, kidneys, and brain cortex, and the expression of neuronal NOS (bNOS) mRNA in brain cortex, were analyzed by RT-PCR/Southern blotting or RNase protection analysis. Administration of aracepril markedly lowered blood pressure and decreased left ventricular weight in SHR-SP/Izm. Expression of ET-1 mRNA in the heart, kidneys, and brain was significantly enhanced in SHR/SP/Izm compared with that in WKY/Izm. Aracepril significantly decreased the expression of ET-1 mRNA, whereas there was no significant change of that in the aorta. Although expression of eNOS mRNA in the heart, aorta, and kidneys did not show any significant difference between the two strains of rats, administration of aracepril for 8 weeks significantly decreased the expression of eNOS and bNOS mRNA in brain tissue. These results suggested that aracepril may protect major target organs by modifying the expression of ET-1 and NOS mRNA, in addition to its hypotensive effect.
Tanabe
A
A
Department of Medicine, Tokyo Women's Medical College, Japan.
Naruse
M
M
Seki
T
T
Adachi
C
C
Yoshimoto
T
T
Imaki
T
T
Naruse
K
K
Demura
R
R
Demura
H
H
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D019332:Endothelin-1 / Q000096:biosynthesis* / Q000235:genetics; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D019001:Nitric Oxide Synthase / Q000096:biosynthesis* / Q000235:genetics; D052250:Nitric Oxide Synthase Type III; D009929:Organ Size / Q000187:drug effects; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D011918:Rats, Inbred SHR; D014018:Tissue Distribution
D000806:Angiotensin-Converting Enzyme Inhibitors; D019332:Endothelin-1; D012333:RNA, Messenger; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat