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SUPPRESSION OF VASCULAR TRANSFORMING GROWTH FACTOR‐β 1 AND EXTRACELLULAR MATRIX GENE EXPRESSIONS BY CILAZAPRIL AND NIFEDIPINE IN HYPERTENSIVE RATS
Author(s) -
Kim Shokei,
Ohta Kensuke,
Hamaguchi Akinori,
Miura Katsuyuki,
Yukimura Tokihito,
Iwao Hiroshi
Publication year - 1995
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.1995.tb02952.x
Subject(s) - cilazapril , endocrinology , medicine , vascular smooth muscle , fibronectin , nifedipine , laminin , muscle hypertrophy , aorta , extracellular matrix , mesenteric arteries , angiotensin ii , artery , angiotensin converting enzyme , chemistry , blood pressure , ace inhibitor , calcium , biochemistry , smooth muscle
Summary 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‐β 1 (TGF‐β 1 ) 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‐β 1 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‐bland 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‐Blmay 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‐Bland extracellular matrix.