Enalapril suppresses normal accumulation of elastin and collagen in cardiovascular tissues of growing rats

Keeley, F. W.; Elmoselhi, Adel; Leenen, F. H. H.

doi:10.1152/ajpheart.1992.262.4.h1013

Cited by 32 publications

(23 citation statements)

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“…19 -21 The concentration of angiotensin II required for an effect in some of these studies was high, 19,20 and possibly not physiological; however, animal data lend support to a potential role for angiotensin II on vascular collagen accumulation. Inhibition of angiotensinconverting enzyme activity suppressed the accumulation of collagen in arteries of growing rats 22 and in spontaneously hypertensive rats. 23 Recently, infusion of angiotensin II into rats was shown to induce aortic fibrosis.…”

mentioning

confidence: 94%

Angiotensin II Stimulates Collagen Synthesis in Human Vascular Smooth Muscle Cells

Ford

Pickering

1999

ATVB

102

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Abstract-Angiotensin II is an established regulator of vascular tone and smooth muscle cell (SMC) growth. However, there are little data about its effect on collagen synthesis by SMCs and none regarding the mechanism of such an effect. We studied the effect of angiotensin II on collagen production by human arterial SMCs, using uptake of [ 3 H]proline into collagenase-digestible proteins, and by ribonuclease protection assay for mRNA encoding the pro␣1 chain of type I collagen, the major collagen in arteries. This revealed a dose-dependent increase in relative collagen synthesis rate and a dose-dependent increase in pro␣1(I) collagen mRNA abundance, with the half-maximal effect at 1.7 nmol/L. Angiotensin II-stimulated collagen expression was associated with a 6-fold increase in transforming growth factor-␤ (TGF-␤) production and was inhibited by a neutralizing antibody to TGF-␤. Both collagen production and TGF-␤ release were inhibited by the AT 1 -specific antagonist, losartan, but not by the AT 2 receptor antagonist, PD123319. To determined if tyrosine phosphorylation was functionally linked to collagen synthesis, we studied the effect of 2 mechanistically distinct inhibitors of tyrosine kinase, genistein, and tyrphostin A25. These inhibitors abrogated angiotensin II-mediated procollagen mRNA expression and angiotensin II-mediated TGF-␤ production, whereas the inactive homolog tyrphostin A1 had no effect. We conclude that angiotensin II stimulates collagen production in human arterial SMCs via the AT 1 receptor and an autocrine loop of TGF-␤, induction of which requires tyrosine phosphorylation.

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confidence: 94%

Angiotensin II Stimulates Collagen Synthesis in Human Vascular Smooth Muscle Cells

Ford

Pickering

1999

ATVB

102

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“…Nonetheless, in mice no hypotensive effect was detected even during chronic treatment with one of the above-mentioned pharmacological agents (22). CEIs could be even more effective in the elderly, based on the favorable effects on cardiovascular fibrosis detected in experimental studies (25). Because the pharmacological effects of the CEI are due to more than one mechanism, mainly inhibition of ANG II formation and blockade of bradykinin metabolism, it was necessary to confirm that these actions are related to blockade of ANG II formation either in the plasma or in the involved tissues.…”

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confidence: 99%

Protective effect of long-term angiotensin II inhibition

Basso¹,

Cini²,

Pietrelli³

et al. 2007

American Journal of Physiology-Heart and Circulatory Physiology

155

114

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Experimental studies indicate that angiotensin II (ANG II) through its type 1 receptor (AT1) promotes cardiovascular hypertrophy and fibrosis. Therefore, the aim of this study was to analyze whether chronic long-term inhibition of the renin-angiotensin system (RAS) can prevent most of the deleterious effects due to aging in the cardiovascular system of the normal rat. The main objective was to compare two strategies of ANG II blockade: a converting enzyme inhibitor (CEI) and an AT1 receptor blocker (AT1RB). A control group remained untreated; treatment was initiated 2 wk after weaning. A CEI, enalapril (10 mg ⅐ kg Ϫ1 ⅐ day Ϫ1 ), or an AT 1RB, losartan (30 mg ⅐ kg Ϫ1 ⅐ day Ϫ1 ), was used to inhibit the RAS. Systolic blood pressure, body weight, and water and food intake were recorded over the whole experimental period. Heart, aorta, and mesenteric artery weight as well as histological analysis of cardiovascular structure were performed at 6 and 18 mo. Twenty animals in each of the three experimental groups were allowed to die spontaneously. The results demonstrated a significant protective effect on the function and structure of the cardiovascular system in all treated animals. Changes observed at 18 mo of age in the hearts and aortas were quite significant, but each treatment completely abolished this deterioration. The similarity between the results detected with either enalapril or losartan treatment clearly indicates that most of the effects are exerted through AT 1 receptors. An outstanding finding was the significant and similar prolongation of life span in both groups of treated animals compared with untreated control animals. losartan; enalapril; heart; aorta; life span THE NATURAL PROCESS OF AGING is related to a progressive modification, and ultimately, a loss of organ function. These alterations are common to all species. In general, there is a correlation between the structural and functional changes associated with aging. In mammals, degenerative processes such as arteriosclerosis, the development of senile plaques in the brain, and the replacement of functional parenchyma by fibroconnective tissue in a variety of organs are considered manifestations of aging (19,41).Ultrastructurally, a reduction in the number of cellular organelles such as mitochondria is common in the aging process (13,21,36). Lifelong free radical production could play a main role in the reduction of the number and in both structural and functional mitochondria modifications (6,20,38). It has been widely postulated that reactive oxygen species (ROS) are causally involved in the aging process (19,20). In this sense, earlier data (4, 17) have confirmed that nitric oxide synthase (NOS) activity in the aorta and nitric oxide (NO) production diminish with age, whereas chronic long-term administration of angiotensin II (ANG II) inhibitors maintains endothelial NOS activity in old animals. Moreover, the mitochondria from hearts of aged rats chronically treated with ANG II inhibitors were found to have increased NOS activity and decrease...

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“…- 39 In the normotensive rat, accumulation of elastin and collagen in the aorta occurs mainly during the first 10 to 12 weeks of life. 39 Although the increase in arterial collagen content seems to be partly related to elevated blood pressure, other factors have been found to stimulate collagen synthesis in hypertensive animals.…”

mentioning

confidence: 99%

“…39 Although the increase in arterial collagen content seems to be partly related to elevated blood pressure, other factors have been found to stimulate collagen synthesis in hypertensive animals. More specifically, Ang II receptor stimulation is able to increase collagen synthesis by acting directly on smooth muscle cells.…”

mentioning

confidence: 99%

Angiotensin converting enzyme inhibition prevents the increase in aortic collagen in rats.

et al. 1994

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Four groups of 4-week-old spontaneously hypertensive rats were treated during 4 months with the angiotensin converting enzyme inhibitor quinapril at 1 mg/kg per day (Ql) or 10 mg/kg per day (Q10), hydralazine at 15 mg/kg per day (H), or placebo (P). In the first set of experiments, blood pressure was measured in conscious rats, and plasma and aortic angiotensin converting enzyme activities were evaluated. In the second set of experiments, histomorphometric parameters of the thoracic aorta were evaluated. Mean blood pressure was lower in the Q10 and H groups (136±16 and 149±11 mm Hg) compared with the P group (190±23 mm Hg) (P<.01). The Ql group showed mean blood pressure values (171 ±15 mm Hg) lower than the P group (P<.05) but significantly higher than the Q10 and H groups (P<.01 and P<.05, respectively). Aortic medial cross-sectional area was significantly lower in the H and Q10 groups (455 ±61 and 487±57 x 10 3 jun 2 ) than in the P group (636±72 /mm of aorta). Aortic angiotensin converting enzyme activity was inhibited by approximately 60% in both groups treated with quinapril, whereas plasma angkrtension converting enzyme activity was reduced only in the Q10 rats. These results show that, whereas both hydralazine and quinapril prevented the development of aortic hypertrophy in a pressure-dependent manner, the prevention of the increase in aortic collagen was observed only after quinapril treatment. This latter effect of angiotensin converting enzyme inhibition was not related to the blood pressure reduction but was associated with the reduction of aortic and not plasma converting enzyme.

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Enalapril suppresses normal accumulation of elastin and collagen in cardiovascular tissues of growing rats

Cited by 32 publications

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Angiotensin II Stimulates Collagen Synthesis in Human Vascular Smooth Muscle Cells

Angiotensin II Stimulates Collagen Synthesis in Human Vascular Smooth Muscle Cells

Protective effect of long-term angiotensin II inhibition

Angiotensin converting enzyme inhibition prevents the increase in aortic collagen in rats.

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