Suppression of vascular transforming growth factor-beta1 and extracellular matrix gene expressions by cilazapril and nifedipine in hypertensive rats.
1. We investigated the protective effects of an angiotensin-converting enzyme inhibitor (ACEI) and a Ca antagonist on vascular injury in hypertension. 2. Thirteen week old stroke-prone spontaneously hypertensive rats (SHRSP) were orally given cilazapril (ACEI 10 mg per kg day) or nifedipine (Ca antagonist 30 mg kg per day) for 12 weeks. After the treatment, the aorta and superior mesenteric artery were excised, and subjected to the extraction of RNA. mRNA levels for the transforming growth factor-beta1 (TGF-beta1) and extracellular matrix components such as fibronectin (FN), collagen type I (CoI), type III (CoIII) and type IV (CoIV) and laminin, were measured by northern blot analysis, using each specific cDNA probe. 3. In the mesenteric artery of SHRSP, TGF-beta1 mRNA levels were increased compared with Wistar-Kyoto (WKY) rats, being accompanied by a significant increase in mRNA levels for FN, CoI, CoIII, CoIV and laminin. In the aorta, only TGF-beta1 and fibronectin mRNAs were increased in SHRSP, but collagen and laminin were not increased. 4. Both cilazapril and nifedipine, to similar extents, suppressed the above mentioned increased gene expressions in both mesenteric artery and aorta, being associated with the improvement of vascular hypertrophy. 5. These results suggest that TGF-beta1 may be responsible for smooth muscle cell hypertrophy and the increased deposition of extracellular matrix in hypertensive blood vessels. Both cilazapril and nifedipine may lessen hypertensive vascular thickening, by suppressing the gene expression of TGF-beta1 and extracellular matrix.
Kim
S
S
Department of Pharmacology, Osaka City University Medical School, Japan.
Ohta
K
K
Hamaguchi
A
A
Miura
K
K
Yukimura
T
T
Iwao
H
H
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001345:Autoradiography; D001808:Blood Vessels / Q000187:drug effects / Q000378:metabolism; D015152:Blotting, Northern; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002561:Cerebrovascular Disorders / Q000235:genetics / Q000503:physiopathology; D017315:Cilazapril / Q000494:pharmacology*; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects*; D008297:Male; D009543:Nifedipine / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D051381:Rats; D011918:Rats, Inbred SHR; D016212:Transforming Growth Factor beta / Q000096:biosynthesis*
D000806:Angiotensin-Converting Enzyme Inhibitors; D002121:Calcium Channel Blockers; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D017315:Cilazapril; D009543:Nifedipine