Cardiovascular risk, renal hypertensive damage, and effects of

Witte, Klaus; Schnecko, Anke; Schmidt, Thomas M.; Voll, Christian; Kränzlin, Bettina

doi:10.1016/s0306-3623(99)00037-3

Cited by 8 publications

(2 citation statements)

References 21 publications

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“…In contrast to heterozygous rats, in our homozygous Ren2 rats, proteinuria if anything was mild. This is presumably due to the early decline in blood pressure to low normotensive values, secondary to early development of heart failure, as blood pressure has been shown to be an important determinant of renal damage in the Ren2 model (Langheinrich et al, 1996;Witte et al, 1999). However, data on proteinuria in our study are not complete and would need confirmation from further studies.…”

Section: Figurementioning

confidence: 70%

Specific MAP-Kinase Blockade Protects against Renal Damage in Homozygous TGR(mRen2)27 Rats

Borst¹,

Navis²,

Boer³

et al. 2003

Laboratory Investigation

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SUMMARY:Angiotensin II (AngII) plays an important role in renal damage by acting on hemodynamics, cell-growth, proliferation, and fibrosis, mainly by effects on the AngII type 1 (AT 1 ) receptor. The AT 1 receptor activates several intracellular signaling molecules such as mitogen-activated protein kinases extracellular signal-regulated kinase (ERK) and p38, but their role in AngII-mediated renal damage is not well characterized. We therefore investigated whether pharmacologic blockade of ERK and p38 could prevent renal damage in high-renin homozygous transgenic rats (Ren2), with the effects of an AT 1 receptor antagonist (AT 1 -RA) as a reference. Seven-week-old homozygous Ren2 rats were treated with low-dose AT 1 -RA candesartan, ERK inhibitor tyrphostin, or p38 inhibitor SB239063 for 4 weeks. Untreated Ren2 and SD rats served as controls. Blood pressure was measured at 7 and 11 weeks. At 11 weeks, plasma renin activity (PRA) and serum aldosterone were determined, and the animals were killed. Kidney sections were scored for glomerular and interstitial smooth muscle actin and glomerular desmin expression as early markers for renal damage. Mesangial matrix expansion was determined as a marker for structural damage. PRA and aldosterone levels were elevated in untreated Ren2 rats in comparison to SD controls. AT 1 -RA further increased PRA but decreased aldosterone. All parameters of renal damage were elevated in untreated Ren2 rats. Blood pressure was not elevated at week 7 in Ren2 and not affected by either treatment. Mild signs of hypertensive damage were found in untreated Ren2 rats. All interventions significantly diminished damage to glomerular epithelium and interstitium. In addition, AT 1 receptor and p38 blockade reduced mesangial matrix expansion. In homozygous Ren2 rats, renal damage was ameliorated by a nonhypotensive dose of an AT 1 -RA and, similarly, by blockade of ERK or p38. This suggests that ERK and p38 are involved in AngII-mediated renal damage. (Lab Invest 2003, 83:1761-1770.

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Section: Figurementioning

confidence: 70%

Specific MAP-Kinase Blockade Protects against Renal Damage in Homozygous TGR(mRen2)27 Rats

Borst¹,

Navis²,

Boer³

et al. 2003

Laboratory Investigation

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“…Good examples of this are motor activity, body temperature and cardiovascular parameters. They are used to characterize an organism in pharmacological and toxicological studies (Witte et al 1999, Gordon & Mack 2001 or to estimate the costs associated with impairing events and stress (Gattermann 1983, Tornatzky & Miczek 1993, Moberg 2000; for a review, see Broom & Johnson 1993). Monitoring of these parameters also allows evaluation of the housing conditions of laboratory animals, thus preventing stress effects and providing good conditions for animal welfare.…”

Section: Discussionmentioning

confidence: 99%

Indicators for post-surgery recovery in Mongolian gerbils (Meriones unguiculatus)

et al. 2005

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SummaryTelemetric investigations of various parameters are widely used to estimate an animal's state. However, the implantation of the transmitters includes anaesthesia and surgery and has short and longer lasting impacts on the studied object. The aim of the present paper was to evaluate these effects in Mongolian gerbils, namely the hypothermia caused by the anaesthetic and the enduring disturbance of daily rhythmicity until complete recovery. The surgery associated with the implantation of the transmitters differed both in severity and type of anaesthesia. Whereas normal values of body temperature were restored within hours, restoration of daily rhythm required several days, depending on the severity of the surgical procedure. Also, the sensitivity of the body temperature to activity changes was different until the rhythms were re-established. A method based on the rhythm magnitude and shape was proposed to estimate the time until complete recovery of the animals.

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Effect of sirolimus on renal ischaemia/reperfusion injury in normotensive and hypertensive rats

Viklický¹,

Böhmová²,

Ouyang³

et al. 2004

Transpl Int

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Renal ischaemia/reperfusion (I/R) injury and hypertension represent major alloantigen-independent factors contributing to the development of chronic allograft nephropathy of renal allografts. In the present study, we investigated the effect of the anti-proliferative immunosuppressant, sirolimus (SIR), in a model of accelerated renal injury in hypertensive transgenic rats (TGRs). Twenty anaesthetized uninephrectomized TGRs with renin overproduction [TGR(mREN2)27] and 20 normotensive Han SD (SD) rats as genetic controls had their renal pedicles clipped for 45 min and were subsequently treated with either SIR (0.5 mg/kg per day, orally) or placebo ( n=10 in each group) for 16 weeks, after which time the kidneys were harvested for morphological and immunohistochemical analysis. High-renin hypertension aggravated the functional and structural changes induced by I/R in SD animals: both SIR-treated and untreated TGRs exhibited significantly greater proteinuria and suffered from more severe glomerulosclerosis ( P<0.01) and vasculopathy ( P<0.01), as well as compensatory renal hypertrophy ( P<0.01) and tissue TGF-beta1 expression, than both normotensive SD groups ( P<0.01). SIR-treated SD rats showed reduced proteinuria ( P<0.01), glomerulosclerosis ( P<0.01), and TGF-beta1 expression in the glomerular epithelium and proximal tubuli ( P<0.05) compared with placebo-treated SD rats. SIR-treated TGRs had significantly lower proteinuria at week 4 after I/R ( P<0.01) than placebo-treated TGRs, but there were no significant differences thereafter. Morphological patterns were similar in treated and untreated TGRs at week 16. High-renin-induced hypertension aggravated the renal injury induced by I/R. Sirolimus treatment ameliorated some late functional and morphological changes induced by I/R injury in hypertensive TGRs but, particularly, in normotensive SD rats.

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Cardiovascular risk, renal hypertensive damage, and effects of

Cited by 8 publications

References 21 publications

Specific MAP-Kinase Blockade Protects against Renal Damage in Homozygous TGR(mRen2)27 Rats

Specific MAP-Kinase Blockade Protects against Renal Damage in Homozygous TGR(mRen2)27 Rats

Indicators for post-surgery recovery in Mongolian gerbils (Meriones unguiculatus)

Effect of sirolimus on renal ischaemia/reperfusion injury in normotensive and hypertensive rats

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