Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.15.1 (ACE)
 18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In genetic and acquired hypertension, a structural remodeling of the nonmyocyte compartment of myocardium, including the accumulation of fibrillar collagen and other components of the extracellular matrix (ECM) within the interstitium, represents a determinant of pathologic hypertrophy that leads to ventricular dysfunction. Therefore, to evaluate the potential benefit of the angiotensin converting enzyme (ACE) inhibitor quinapril in reversing the interstitial remodeling in spontaneously hypertensive rats (SHR) with established left ventricular hypertrophy (LVH), we treated 16-week-old male SHR with oral quinapril (average dose, 10 mg/kg body weight/day) for 20 weeks. Interstitial fibrosis was determined morphometrically using an automatic image analyzer. The amount of collagen was evaluated by measuring myocardial hydroxyproline concentration. Myocardial deposition of collagen molecules (types I, III, and IV) and other ECM components (fibronectin, laminin) was analyzed by immunohistochemical techniques using specific monoclonal antibodies. The activity of ACE was measured in left ventricular tissue by a fluorometric assay. In quinapril-treated SHR compared with 36-week-old untreated SHR and age- and sex-matched Wistar-Kyoto (WKY) controls, we found 1) a lesser degree of LVH and a lesser level of blood pressure, 2) a lesser degree of interstitial fibrosis, represented by less interstitial collagen volume fraction (5.73 +/- 0.45% v 3.42 +/- 0.28%, P < .05; WKY, 3.44 +/- 0.66%), 3) a lower hydroxyproline concentration (1.09 +/- 0.05 mumol/L/g dry weight/100 g body weight to 0.81 +/- 0.05 mumol/L/g dry weight/100 g body weight, P < .05; WKY, 0.96 +/- 0.06 mumol/L/g dry weight/100 g body weight), 4) a lesser presence of collagen fibers, and 5) a lesser presence of collagen IV, fibronectin, and laminin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Quinapril decreases myocardial accumulation of extracellular matrix components in spontaneously hypertensive rats. 757 98

The aim of our study was to investigate bone morphogenetic protein-7 (BMP-7) expression in a rat model of chronic cyclosporine (CsA) toxicity compare with healthy controls, as well as the influence of treatment with the angiotensin-converting enzyme inhibitor (ACEI) quinapril. Twenty-four male Wistar rats were divided into groups of eight animals treated with CsA (15 mg/kg intraperitoneally) for 8 weeks (CsA group) without or with quinapril (10 mg/kg per day in the drinking water: CsA group + Q) for comparison with healthy controls (H group). The renal tissues were examined by light microscopy for CsA toxicity; specifically, tubulointerstitial damage and afferent arteriolopathy as well as BMP-7 expression were semiquantitatively scored by immunohistochemical staining. Mean CsA levels were 1982 ng/mL and 1968 ng/mL for the CsA and CsA + Q groups, respectively. At the end of the study period, the mean serum creatinine levels were 0.8 +/- 0.2 mg/dL, 1.6 +/- 0.8 mg/dL, and 1.4 +/- 0.8 mg/dL for the H, CsA, and CsA + Q groups, respectively. Interstitial fibrosis, tubular atrophy, and afferent arteriolar hyalinization were present in the CsA group and, to a lesser degree, in the CsA + Q group, compared with the H group. CsA-treated rats displayed significantly decreased BMP-7 expression compared with healthy controls (P <.0005). BMP-7 expression was higher among the CsA + Q group than the the group CsA group. In a rat model histologic changes characteristic of CsA-induced nephrotoxicity are associated with decreased expression of BMP-7, which seems to be at least partially restored by ACE inhibition.
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PMID:Cyclosporine-A induced nephrotoxicity is associated with decreased renal bone morphogenetic protein-7 expression in rats. 1501 23