Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0920646 (renal ischemia)
 2,515 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of ketanserin (Kt) has been analyzed during the development of two-kidney-two-clip (2k-2c) renovascular hypertension in the rat. Male Wistar rats were divided into four experimental groups: (1) clip Kt (ClKt) (n = 12)--A silver clip (0.25 mm width) was placed in each renal artery 3 days after beginning the administration of Kt (10 mg/kg/day) in the drinking water; (2) sham Kt (ShKt) (n = 13)--Similar to group 1, but the clips were placed in, and immediately removed from, the renal arteries; (3) untreated clip (UCl) (n = 10)--Similar to group 1, but the rats drank water; (4) untreated sham (USh) (n = 10)--Similar to group 2, but the rats drank water. Blood pressure (BP) was measured before surgery and was followed weekly for 7 weeks. At the end of this period, blood and cerebrospinal fluid (CSF) samples were obtained in all the animals. Plasma renin activity (PRA) and plasma and CSF angiotensinogen concentration (AoC) were evaluated. The results have shown that Kt partially inhibited the increase in BP induced by bilateral renal ischemia (BP: UCl rats 180.5 +/- 12.4 versus ClKt rats 149.8 +/- 5.1 mm Hg; p less than 0.01; USh rats 116.7 +/- 3.7; ShKt rats 114.4 +/- 5.0 mm Hg). PRA was similar in hypertensive and control rats whether or not they had received Kt. AoC in plasma was decreased in clipped treated and untreated rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Chronic administration of ketanserin and the development of two-kidney-two-clip Goldblatt renovascular hypertension in the rat. 244 74

The effect of chronic hypobaric hypoxia (CHH) on the development of 2k-2c Goldblatt renovascular hypertension has been analyzed in rats of both sexes. Results have shown lower values of blood pressure (BP) in all the animals exposed to CHH compared with their normoxic control (P < 0.001). Haematocrit was increased by adaptation to CHH (P < 0.001), and was larger in male than in female hypoxic rats, both normotensive (P < 0.05) and hypertensive (P < 0.01). Plasma renin activity was higher in normoxic and hypoxic hypertensive female rats than in their normotensive controls (P < 0.05). Plasma angiotensinogen concentration was higher in normoxic control male rats than in all the other groups. This difference disappeared after adaptation to CHH or development of hypertension. Plasma aldosterone concentration was lowest in normoxic control male rats and the difference also disappeared after CHH or renal ischemia. Present data indicate that CHH blunts the hypertensive response to bilateral renal ischemia in male and female rats. Sexual differences related to the mechanisms that could be involved in hypertension development have been observed. The renin-angiotensin-aldosterone system might be modulated by gonadal hormones during the development of hypertension.
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PMID:Changes in the renin-angiotensin-aldosterone system in 2 kidney -2 clip Goldblatt hypertensive rats of both sexes submitted to chronic hypobaric hypoxia. 800 44

Some reports have stated that central norepinephrine (NE) depletion inhibited the development of hypertension in the rat. On the other hand, this pharmacological treatment induces changes on the central renin-angiotensin system. The present study was designed to follow the development of 2 kidney-2 clip (2k-2c) renovascular hypertension in rats depleted of central NE and to analyze the central and peripheral renin-angiotensin system. Male Wistar rats (n = 40) were used. Half of the animals was injected, intracisternally, with 6-hydroxydopamine (6-OHDA), the remaining rats only received the vehicle. One week later a silver clip was placed on each renal artery on half of the 6-OHDA treated rats and on half of the vehicle treated animals. A sham operation was performed on the remaining rats. Blood pressure was measured weekly during 7 weeks. Then, blood and cerebrospinal fluid (CSF) samples were obtained. The brain was dissected in several areas. NE and angiotensinogen concentration (AoC) were determined in tissue samples. AoC was evaluated in plasma and CSF; plasma renin activity was also measured. Hypertension development was not prevented by central NE depletion, which was significant in all central areas (p < 0.001). Other significant results showed that renal ischemia and/or NE depletion induced a significant increase in angiotensinogen concentration in the hypothalamus (p < 0.01) and in CSF (p < 0.05). In summary: central NE depletion was not able to modify the development of 2 k - 2 c hypertension. Treatment and renal ischemia induced an increase of central AoC.
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PMID:Effect of central norepinephrine depletion on renovascular hypertension and on the renin system. 837 8

The aim of the present study was to provide an overview of the role of circulating gonadal steroids on the adaptive changes of the renin-angiotensin system to chronic hypobaric hypoxia (CHH: 4400 m simulated altitude in an hypobaric chamber) and the development of experimental hypertension by bilateral renal ischemia. In order to fulfill this goal, blood pressure (BP), plasma renin activity (PRA) and plasma angiotensinogen concentration (PAoC) as well as haematocrit (Htc) and body weight (BW) of intact and post-puberal castrated normotensive (Nt) and hypertensive (Ht) rats of both sexes were studied following an experimental design similar to that of previous works. Post-puberal castration decreased BP of Nt and Ht rats subjected to CHH. Sexual dimorphism in BP, PRA and PAoC was maintained while that in haematocrit disappeared after castration. Results suggest that circulating sexual steroid hormones are involved in the response of the renin-angiotensin system to the experimental conditions of environmental reduced O2 partial pressure.
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PMID:Effect of castration on renin-angiotensin system of hypertensive rats submitted to chronic hypobaric hypoxia (simulated altitude: 4400 m). 943 79

The present studies determined the effect of renal ischemia/reperfusion on components of the intrarenal renin-angiotensin system in rats and evaluated the effect of AT1 angiotensin (ANG) II receptor blockade on functional recovery. After bilateral renal pedicle occlusion for 60 min, serum creatinine increased, peaking at 72 h, and returned to sham levels after 120 h. ANG II levels in ischemic kidneys were significantly increased 24 h after reperfusion but did not differ from levels in sham kidneys after 120 h. Both renal cortical angiotensinogen mRNA and proximal tubular AT1 receptor mRNA were significantly reduced early after reperfusion, returning to sham levels by 120 and 72 h, respectively. AT2 ANG II receptor mRNA was undetectable in proximal tubules from sham rats but was consistently present in ischemic rats at 120 h. By histoautoradiography, we found that binding of 125I-labeled ANG II was preserved in glomeruli but was decreased in whole cortex and outer medulla early after reperfusion and was completely blocked by the AT1 antagonist losartan. Treatment of rats with losartan (25 mg/kg s.c. daily), starting at the time of reperfusion, had no effect on expression of proliferating cell nuclear antigen in cortical tubules but caused a significant decrease in serum creatinine at 72 h (ischemia: 334 +/- 69 microM vs. ischemia + losartan: 135 +/- 28 microM; P < 0.025, n = 6). These data indicate that renal ischemic injury causes an early increase in intrarenal ANG II levels, associated with reduction of mRNA for angiotensinogen and proximal tubular AT1 receptors, and maintenance of glomerular ANG II binding. Losartan accelerates recovery of renal function, suggesting that activation of AT1 receptors impairs glomerular filtration in the postischemic kidney.
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PMID:Role of AT1 angiotensin II receptors in renal ischemic injury. 945 26

Autosomal dominant polycystic kidney disease (ADPKD), a common genetic disease, is characterized by the development of hypertension and end stage renal disease. An increase in the activity of the renin-angiotensin system, due to a renal ischemia caused by cyst expansion, contributes to the development of hypertension and renal failure in ADPKD. Recently, the angiotensinogen (AGT) gene, M235T, and angiotensin II type 1 receptor (ATR) gene, A1166C, polymorphisms have been associated with the susceptibility to develop hypertension and renal disease. We hypothesized that the AGT M235T and ATR A1166C polymorphisms could account for some of the variability in the progression of ADPKD. Genotyping was performed in 108 adult patients with ADPKD, and 105 normotensive healthy controls, using PCR and restriction digestion. We analyzed the effects of the AGT M235T and ATR A1166C polymorphisms on hypertension and age at the end stage renal disease (ESRD). Of the 108 patients with ADPKD, 64 (59%) had hypertension and 24 (22%) reached the ESRD. The prevalence of hypertension were; [MM+MT], [TT] genotypes, 60%, 59% (p=1.00); [AA], [AC+CC] genotypes, 60%, 50% respectively (p=0.54). The ages at the onset of ESRD were; [MM+MT], [TT] genotypes, 50 +/- 9 years, 56 +/- 8 years (p=0.07); [AA], [AC+CC] genotypes, 54 +/- 8 years, 52 +/- 14 years, respectively (p=0.07). There were no differences in the prevalence of hypertension and the ages at the ESRD in relation to the AGT M235T and ATR A1166C polymorphisms. We suggest that the AGT and ATR gene polymorphisms would not have an effect on hypertension or the ESRD in ADPKD.
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PMID:Angiotensinogen and angiotensin II type 1 receptor gene polymorphism in patients with autosomal dominant polycystic kidney disease: effect on hypertension and ESRD. 1295 Jan 20

Current national guidelines have recommended the use of renin-angiotensin system inhibitors, including angiotensin II type 1 receptor blockers (ARBs), in preference to other antihypertensive agents for treating hypertensive patients with chronic kidney disease. However, the mechanisms underlying the renoprotective effects of ARBs are multiple and complex. Blood pressure reduction by systemic vasodilation with an ARB contributes to its beneficial effects in treating kidney disease. Furthermore, ARB-induced renal vasodilation results in an increase in renal blood flow, leading to improvement of renal ischemia and hypoxia. ARBs are also effective in reducing urinary albumin excretion through a reduction in intraglomerular pressure and the protection of glomerular endothelium and/or podocyte injuries. In addition to blocking angiotensin II-induced renal cell and tissue injuries, ARBs can decrease intrarenal angiotensin II levels by reducing proximal tubular angiotensinogen and production of collecting duct renin, as well as angiotensin II accumulation in the kidney. In this review, we will briefly summarize our current understanding of the pharmacological effects of an ARB in the kidney. We will also discuss the possible mechanisms responsible for the renoprotective effects of ARBs on type 2 diabetic nephropathy.
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PMID:Angiotensin II blockade and renal protection. 2317 16

Acute kidney injury (AKI) is an important risk factor for incident chronic kidney disease (CKD). Clinical studies disclose that ensuing CKD progresses after functional recovery from AKI, but the underlying mechanisms remain illusive. Using a murine model representing AKI-CKD continuum, we show angiotensin II type 1a (AT1a) receptor signaling as one of the underlying mechanisms. Male adult CD-1 mice presented severe AKI with 20% mortality within 2 weeks after right nephrectomy and left renal ischemia-reperfusion injury. Despite functional recovery, focal tubular atrophy, interstitial cell infiltration and fibrosis, upregulation of genes encoding angiotensinogen and AT1a receptor were shown in kidneys 4 weeks after AKI. Thereafter mice manifested increase of blood pressure, albuminuria and azotemia progressively. Drinking water with or without losartan or hydralazine was administered to mice from 4 weeks after AKI. Increase of mortality, blood pressure, albuminuria, azotemia and kidney fibrosis was noted in mice with vehicle administration during the 5-month experimental period. On the contrary, these parameters in mice with losartan administration were reduced to the levels shown in control group. Hydralazine did not provide similar beneficial effect though blood pressure was controlled. These findings demonstrate that losartan can reduce ensuing CKD and mortality after functional recovery from AKI.
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PMID:Losartan reduces ensuing chronic kidney disease and mortality after acute kidney injury. 2767 27

One of the major obstacles to prevent AKI-CKD transition is the lack of effective methods to follow and predict the ongoing kidney injury after an AKI episode. In the present study, we test the utility of urinary angiotensinogen (UAGT) for dynamically evaluating renal structural changes and predicting AKI-CKD progression by using both mild and severe bilateral renal ischemia/reperfusion injury mice. UAGT returns to pre-ischemic levels 14 days after mild AKI followed by kidney architecture restoration, whereas sustained increase in UAGT accompanies by ongoing renal fibrosis after severe AKI. UAGT at day 14-42 correlates with renal fibrosis 84 days after AKI. For predicting fibrosis at day 84, the area under receiver operating characteristics curve of UAGT at day 14 is 0.81. Persistent elevation in UAGT correlates with sustained activation of intrarenal renin-angiotensin system (RAS) during AKI-CKD transition. Abrogating RAS activation post AKI markedly reduced renal fibrosis, with early RAS intervention (from 14 days after IRI) more beneficial than late intervention (from 42 days after IRI) in alleviating fibrosis. Importantly, UAGT decreases after RAS intervention, and its level at day 14-28 correlates with the extent of renal fibrosis at day 42 post RAS blockade. A pilot study conducted in patients with acute tubular necrosis finds that compared with those recovered, patients with AKI-CKD progression exhibits elevated UAGT during the 3-month follow-up after biopsy. Our study suggests that UAGT enables the dynamical monitoring of renal structural recovery after an AKI episode and may serve as an early predictor for AKI-CKD progression and treatment response.
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PMID:Urinary angiotensinogen predicts progressive chronic kidney disease after an episode of experimental acute kidney injury. 3042 69