Effects of captopril or nitrendipine on left ventricular collagen or laminin B2 gene expression.
A study was designed to clarify the effects of captopril (CAP) or nitrendipine (NITR) on cardiac hypertrophy and left ventricular expression of the laminin B2 or collagen (COL) gene in spontaneously hypertensive rats (SHRs). Cardiac weight was significantly increased in 20-week-old SHRs. Gene expression of the alpha 1 chain of type IV COL determined by northern blot analysis decreased with age in Wistar-Kyoto rats and SHRs. Left ventricular laminin B2 mRNA was decreased at 12 weeks and increased again at 20 weeks in both strains. Daily oral administration of CAP (40 mg/kg, n = 5) or NITR (30 mg/kg, n = 4) to SHRs from 8 to 20 weeks decreased blood pressure to 142 mmHg (p < 0.01 vs 197 mmHg in controls, n = 5). Cardiac weight was 1.26 +/- 0.04 (SE) g in controls and was reduced to 1.03 +/- 0.05 g (p < 0.01) by CAP, but not by NITR (1.24 +/- 0.04). Left ventricular laminin B2 gene expression was attenuated by CAP and NITR to 41% and 32% of the control value, respectively. CAP significantly decreased left ventricular alpha 1 type IV COL mRNA to 11% of the control level, whereas NITR caused a reduction only to 75%. CAP also decreased alpha 1 or alpha 2 type I COL mRNA. These results suggest that angiotensin converting enzyme inhibitors prevent and/or cause regression of cardiac hypertrophy by inhibiting the gene expression of extracellular matrix, and that angiotensin II may have a pivotal role in cardiac hypertrophy.
Katayama
S
S
Fourth Department of Medicine, Saitama Medical School, Japan.
Abe
M
M
Inaba
M
M
Itabashi
A
A
Ishii
J
J
D000818:Animals; D002216:Captopril / Q000494:pharmacology*; D006332:Cardiomegaly / Q000378:metabolism; D003094:Collagen / Q000235:genetics*; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects*; D006321:Heart / Q000187:drug effects*; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism; D007797:Laminin / Q000235:genetics*; D009206:Myocardium / Q000378:metabolism*; D009568:Nitrendipine / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D007797:Laminin; D012333:RNA, Messenger; D003094:Collagen; D009568:Nitrendipine; D002216:Captopril