The Morphology of Juxtaglomerular Cell Hyperplasia and Hypertrophy in Normotensive Rats and Monkeys Given an Angiotensin II Receptor Antagonist

Owen, Roger A.; Molon-Noblot, S; Hubert, Marie-Françoise; Kindt, Maddalena; Keenan, Kevin P.; Eydelloth, R. S.

doi:10.1177/019262339502300319

Cited by 25 publications

(35 citation statements)

References 10 publications

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“…Losartan, a well known specific antagonist of the angiotensin II AT 1 receptor, induces JG cell hypertrophy and hyperplasia (23) and increases the expression of renin mRNA in the kidney several fold (24). In our experiments carried out with glomeruli-containing AA, losartan increased the expression of cGK II and renin mRNA (Fig.…”

Section: Resultsmentioning

confidence: 56%

Expression of type II cGMP-dependent protein kinase in rat kidney is regulated by dehydration and correlated with renin gene expression.

Gambaryan¹,

Häusler²,

Markert³

et al. 1996

J. Clin. Invest.

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AbstractcGMP-based regulatory systems are vital for counteracting the renin-angiotensin system (RAS) which promotes volume expansion and high blood pressure. Natriuretic peptides and nitric oxide acting through their second messenger cGMP normally increase natriuresis and diuresis, and regulate renin release; however, the severe pathological state of cardiac heart failure is characterized by elevated levels of atrial natriuretic peptide that are no longer able to effectively oppose exaggerated RAS effects. There is presently limited information on the intracellular effectors of cGMP actions in the kidney. Recently we reported the cloning of the cDNA for type II cGMP-dependent protein kinase (cGK II), which is highly enriched in intestinal mucosa but was also detected for the first time in kidney. In the present study, cGK II was localized to juxtaglomerular (JG) cells, the ascending thin limb (ATL), and to a lesser extent the brush border of proximal tubules. An activator of renin gene expression, the angiotensin II type I receptor inhibitor, losartan, increased cGK II mRNA and protein three to fourfold in JG cells. In other experiments, water deprivation increased cGK II mRNA and protein three to fourfold in the inner medulla where both cGK II, and a kidney specific Cl

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Section: Resultsmentioning

confidence: 56%

Expression of type II cGMP-dependent protein kinase in rat kidney is regulated by dehydration and correlated with renin gene expression.

Gambaryan¹,

Häusler²,

Markert³

et al. 1996

J. Clin. Invest.

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show abstract

“…These proliferative changes in the afferent arteriolar walls are quite different from the changes that have been observed in other hypertensive, inflammatory or drug-induced vascular lesions. In the 1980s and 1990s, several patho-toxicological studies using rats and monkeys reported that the angiotensin-converting enzyme inhibitor (ACEI) captopril 29,30 and ARBs such as losartan potassium 5,31 commonly induced JGA hyperplasia and afferent arteriolar thickening; 4,5,29,31 however, those studies did not describe the arteriolar changes at a minute level.…”

Section: Discussionmentioning

confidence: 99%

Changes in renal vessels following the long-term administration of an angiotensin II receptor blocker in Zucker fatty rats

Nakanishi

Nagai

Piao

et al. 2011

J Renin Angiotensin Aldosterone Syst

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Introduction:The nephro-protective effects of angiotensin II receptor blockers (ARBs) are widely known; however, there are few reports of long-term effects focusing on the renal vessels. We studied afferent arteriolar changes induced by the long-term administration of an ARB. Materials and Methods: Thirty-two 6-week-old male Zucker fatty rats (ZFRs) were divided into following four groups (n = 8 in each): ZFR Group and ZFR+High Group fed a standard or high-salt diet, respectively; ZFR+ARB Group and ZFR+High+ARB Group fed a standard or high-salt diet with ARB (Olmesartan, 5 mg/kg/day), respectively. Blood pressure, proteinuria, morphological examinations and glomerular haemodynamics in vivo were studied. Results: Marked proliferative changes in the afferent arteriolar smooth muscle cells (SMCs) were frequently observed in the two groups given ARBs; in the ZFR+ARB group (77.3±10.3%) compared with the two groups without ARB (1.7%, p < 0.005; 1.2%, p < 0.0005) and 37.4±15.6% in the ZFR+High+ARB group. Proteinuria markedly decreased in the groups treated with ARBs, but the glomerular erythrocyte velocities showed no differences. Conclusions: Our findings indicate that long-term ARB administration induced unusual proliferative changes in SMCs of afferent arterioles of ZFRs. These changes could narrow arteriolar lumens and reduce intraglomerular pressure, but they could cause also irreversible damage to the arterioles.

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“…[1][2][3][4][5] We have reported that Zucker fatty rats (ZFRs) presented with unusual proliferative changes of smooth muscle cells (SMCs) in afferent arteriolar walls and an extreme increase in renin-producing cells following long-term oral administration of ARB. 6 ARBs are widely used in adult patients with hypertension and kidney diseases.…”

Section: Introductionmentioning

confidence: 99%

Proliferative changes of renal arteriolar walls induced by administration of angiotensin II receptor blocker are frequent in juvenile rats

Nagai

Nakanishi

Akimoto

et al. 2013

J Renin Angiotensin Aldosterone Syst

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Introduction: Our previous study of angiotensin II receptor blocker (ARB) administration in rats induced unusual proliferative changes of smooth muscle cells in renal arteriolar walls. The present study examined if the incidence of the changes depended on the rats' age, and how long it would take to find changes. Materials and methods: Six-week-old (juvenile spontaneous hypertensive rats (SHRs)+ARB group, n=15) and 20-week-old (adult SHRs+ARB group, n=10) male SHRs were fed a standard diet (0.4% NaCl) containing valsartan (10 mg/kg/day; Novartis Co.). Fifteen age-matched SHRs were studied as controls. After 4, 8, and 12 weeks, the rat kidneys were examined under light and electron microscopes and through immunohistochemical studies. Results: Extremely concentric proliferative changes in afferent arteriolar walls were frequently observed in the juvenile SHR+ARB group compared to the adult SHR+ARB group (48.7±6.8% vs 19.3±6.9%; p=0.0307) at the 12 th week. Increased renin expression and arteriolar changes were found from the 4 th week in the juvenile SHR+ARB group. Conclusion: This study indicates that ARB administration induces unusual proliferative changes and a marked reninproducing cell increase in afferent arterioles more frequently in juveniles than adult rats. It is suggested that the treatment of ARB in juveniles might have a higher risk of changes in renal afferent arterioles.

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The Morphology of Juxtaglomerular Cell Hyperplasia and Hypertrophy in Normotensive Rats and Monkeys Given an Angiotensin II Receptor Antagonist

Cited by 25 publications

References 10 publications

Expression of type II cGMP-dependent protein kinase in rat kidney is regulated by dehydration and correlated with renin gene expression.

Expression of type II cGMP-dependent protein kinase in rat kidney is regulated by dehydration and correlated with renin gene expression.

Changes in renal vessels following the long-term administration of an angiotensin II receptor blocker in Zucker fatty rats

Proliferative changes of renal arteriolar walls induced by administration of angiotensin II receptor blocker are frequent in juvenile rats

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