Reference

Effect of ramipril and losartan on collagen expression in right and left heart after myocardial infarction

Effect of ramipril and losartan on collagen expression in right and left heart after myocardial infarction. Dixon, Ian M. C.; Ju, Haisong; Jassal, Davinder S.; Peterson, David J. ( Molecular Cardiology Lab., Univ. Manitoba, Winnipeg, MB R2H 2A6, Can.). Molecular and Cellular Biochemistry, 165(1), 31-45 (English) 1996 Kluwer. CODEN: MCBIB8. ISSN: 0300-8177. DOCUMENT TYPE: Journal CA Section: 14 (Mammalian Pathological Biochemistry) Section cross-reference(s): 1 Although increased deposition of collagen proteins has been described after myocardial infarction (MI), little is known of time-dependent transcriptional alteration of specific cardiac collagen sub-types as well as the degradative mechanisms for cardiac collagens in right and left ventricular myocardium remote to large left ventricular infarction.Some commonly used reagents like 114798-26-4 and 9015-94-5 are used in this experiment. We sought to study collagen mRNA abundance and the deposition of specific collagen subtypes in noninfarcted left and right rat heart muscle at different times after MI. We also assessed the activity of different myocardial matrix metalloproteinases (MMP) using zymog. to gain some information about degradative pathways for collagen. Furthermore, we assessed passive compliance properties of the right ventricle in exptl. hearts. Finally we investigated the role of the renin angiotensin system in the collagen gene expression by administration of an angiotensin converting enzyme (ACE) inhibitor (ramipril) and an angiotensin II receptor type I antagonist (losartan) in exptl. animals. We obsd. that the mRNA abundance of types I and III collagen were increased 3 days after myocardial infarction in both viable left and uninfarcted right ventricular tissues, that they peaked at 7-14 days, and were maintained at relatively high levels in the 28 and 56 days exptl. groups. Stiffness of the right ventricular myocardium was significantly increased in the 56 days exptl. group when compared to that of control values. These findings correlated with increased immunohistochem. staining patterns of different collagen species in the surviving right (and left) cardiac interstitium of 14, 28, and 56 day exptl. cardiac groups. The elevation of fibrillar collagen mRNA abundance in noninfarcted muscle from ventricular chambers was not significantly altered after treatment of exptl. animals with ramipril and losartan for up to 14 days. MMP activity was increased in viable left ventricle at 14, 28 and 56 days and at 14 days in the right ventricle in exptl. animals when compared to controls. These results indicated that (1) activation of transcription of collagen types I and III gene occurs in acute and chronic MI, and that fibrillar collagen proteins are deposited in the noninfarcted cardiac interstitium after a lag period relative to increased corresponding mRNA abundance; (2) an increase in MMP activity in chronic exptl. hearts indicates that increased collagen deposition may be due to an increment in collagen synthesis rather by reduced degrdn. of collagen, and that MMP activation may be important in remodeling of the noninfarcted cardiac stroma; (3) an increase of right ventricular stiffness was assocd. with increased deposition of collagen; (4) as losartan treatment is not assocd. with any normalization of elevated collagen mRNA abundance, the upregulation of collagen gene expression in this model is not mediated by AT1 receptor; and (5) the redn. of cardiac fibrosis mediated by ACE inhibition and losartan treatment may reside at the post-translational level in cardiac collagen metab. .

The diversified pharmacology of angiotensin II-receptor blockade

The diversified pharmacology of angiotensin II-receptor blockade. Timmermans, Pieter B. M. W. M.; Smith, Ronald D. (DuPont Merck Research Laboratories, Wilmington, DE, USA). Blood Pressure, Supplement, (2, Angiotensin II Receptors), 53-61 (English) 1996 Scandinavian University Press. CODEN: BPSUEY. ISSN: 0803-8023. DOCUMENT TYPE: Journal; General Review CA Section: 1 (Pharmacology) Section cross-reference(s): 2 A review, with 112 refs. The discovery of orally active nonpeptide angiotensin II (A II)-receptor antagonists has initiated a growing understanding of the physiol. and pathophysiol.In this article, certain chemicals are used. One of their cas registry numbers is 114798-26-4 roles of A II. Losartan is the first of the new class of antagonists that block all the well-known effects of A II, including vasoconstriction, aldosterone release, renin release (neg. feedback), and the stimulation of thirst. A II-receptor subtypes have been described, with losartan antagonism defining the AT1 subtype and with PD123319 antagonism defining the AT2 subtype. The AT1 receptor is G-protein-coupled, involving PLC, PLA2, PLD, or adenylate cyclase and the release of intracellular calcium. The receptor-response coupling of the AT2 site remains elusive but may involve protein tyrosine phosphatase and subserve an antiproliferative role. Losartan as the prototype of an AT1-selective antagonist: (i) inhibits A II binding, (ii) antagonizes effects of A II in vivo and in vitro, and (iii) lowers blood pressure in models of A II-dependent hypertension. A II stimulates growth in vitro (DNA and protein synthesis) and in vivo (cardiac and vascular hypertrophy), and these effects are blocked by losartan. Losartan, like angiotensin-converting enzyme inhibitors, has significant renal, cardiac, and cerebral protective effects in models of renal failure, cardiac failure, and stroke, confirming the pathol. role of A II in these models. The pioneering studies in exptl. animals are being confirmed by a growing no. of other AT1-selective blockers and provide the basis of use of losartan for hypertension and its clin. trial in other disease states. .