Tissue Angiotensin-Converting Enzyme Activity Plays an Important Role in Pressure Overload–Induced Cardiac Fibrosis in Rats

Abstract

It has been widely assumed that the cardiac angiotensin-generating system plays an important role in the development and maintenance of cardiac remodeling caused by pressure overload. The roles of angiotensin-converting enzyme (ACE) in pressure overload-induced cardiac hypertrophy and fibrosis in rats were investigated. Pressure overload was achieved by constricting the abdominal aorta above the renal arteries. After they underwent surgery, the rats were treated with a low or high dose of the ACE inhibitor imidapril (0.07 and 0.7 mg/kg/d s.c.) with an osmotic pump for 4 weeks. High-dose imidapril prevented the increase in blood pressure, cardiac hypertrophy, and fibrosis. Low-dose imidapril inhibited only cardiac fibrosis. ACE activity in the myocardium, but not in serum, was significantly increased in the rats with the banded aorta, and ACE immunoreactivity was increased in the areas of fibrosis. These changes were markedly reduced by both doses of imidapril. These results suggest that the increased local ACE expression contributes to the development of pressure overload-induced cardiac fibrosis but is not responsible for hypertrophy in rats.

Pressure-independent effects of pharmacological stimulation of soluble guanylate cyclase on fibrosis in pressure-overloaded rat heart

“…It is noted that BAY 41-2272 administration to AC rats has been shown to lower ACE gene expression and its activity, a main enzyme for Ang II generation in rats. 34,35 Accordingly, this compound decreased the AC-induced increase of Ang II concentration in the LV. Consistent with earlier reports, 34,35 ACE immunoreactivity showed increased distribution in the perivascular and interstitial fibroblasts of pressure-overloaded LV, whereas the distribution was diminished by BAY 41-2272 treatment.…”

“…34,35 Accordingly, this compound decreased the AC-induced increase of Ang II concentration in the LV. Consistent with earlier reports, 34,35 ACE immunoreactivity showed increased distribution in the perivascular and interstitial fibroblasts of pressure-overloaded LV, whereas the distribution was diminished by BAY 41-2272 treatment. Various stimuli have been shown to stimulate ACE synthesis in the cardiovascular system, 36,37 in which activity was increased during myofibroblast transformation in cultured cardiac fibroblasts.…”

Sardine Peptide with Angiotensin I-Converting Enzyme Inhibitory Activity Improves Glucose Tolerance in Stroke-Prone Spontaneously Hypertensive Rats

“…SP contains a wide variety of peptides, among which VY is a predominant ACE inhibitory peptide. 15,30) It has also been confirmed that VY is resistant to gastrointestinal proteases. 34) Matsui et al demonstrated that VY treatment induced a reduction in blood pressure in SHRs and that the target site of VY was the abdominal aorta and kidney.…”

“…28,29) On the one hand, in chronic administration of an inhibitor, no reduction in ACE activity is observed in the serum, but one is observed in the aorta, mesentery, and kidney. 30,31) In addition, SHRSPs show a high level of tissue ACE activity and a high AII concentration, but serum ACE activity and AII concentrations in SHRSPs are considerably lower than those of WKYs. 32,33) The SHRSPs bred in our laboratory showed upregulation of ACE activity in the aorta and mesentery, which is SHRSPs were fed tap water, water containing SP (1 gÁkg À1 Ád À1 ), or captopril (8 mgÁkg À1 Ád À1 ) from 10 weeks of age.…”

Stromal Cell Biology - A Way to Understand the Evolution of Cardiovascular Diseases -

“…Immunoreactivity of angiotensin-converting enzyme (ACE) was increased and distributed in the perivascular and interstitial fibroblasts of the pressure-overloaded rat left ventricle (Figure 3). 86, 88 Various stimuli have been shown to stimulate ACE synthesis in the cardiovascular system, 89,90 in which activity was increased during myofibroblast transformation in cultured cardiac fibroblasts. 91 Activated macrophages also produce ACE, 92 but chymase in mast cells appears to be more responsible for generating Ang II formation in humans.…”