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Bernardo Rodriguez-Iturbe

Publications and source records attributed to Bernardo Rodriguez-Iturbe.

24 records · Page 2Linked to original sources
PubMed2003

Tubulointerstitial disease: role of ischemia and microvascular disease.

PURPOSE OF REVIEW: Tubulointerstitial injury is characteristic of aging-associated renal injury and progressive renal disease. Salt-sensitive hypertension is also associated with tubulointerstitial inflammation, especially when accompanied by microvascular disease. Here we summarize recent studies on the pathogenesis and consequences of tubulointerstitial disease, emphasizing the role of ischemia and the microvasculature. RECENT FINDINGS: Tubulointerstitial injury occurs via several mechanisms of which one of the most important is chronic ischemia. Recent studies suggest that chronic vasoconstriction may contribute to the renal injury associated with angiotensin II, catecholamines, nitric oxide inhibition, hypokalemia, hyperuricemia, and cyclosporine nephropathy. Salt-sensitivity may result as a consequence of the tubulointerstitial inflammatory response to these conditions, and this appears to be perpetuated by the development of preglomerular vascular disease. With progression of tubulointerstitial disease there is also a loss of peritubular capillaries, and stimulating microvascular growth with angiogenic factors can stabilize renal function in these models. SUMMARY: Ischemia secondary to vasoconstriction or to structural changes of the renal vasculature may have important consequences both in terms of mediating salt-sensitive hypertension and renal progression. Angiogenic factors may have potential benefit in preventing or treating these conditions.

Animals↗
PubMed2003

Antioxidant-rich diet relieves hypertension and reduces renal immune infiltration in spontaneously hypertensive rats.

Previous studies have demonstrated that oxidative stress contributes to hypertension and treatments with either antioxidant or immunosuppressive/anti-inflammatory agents improve hypertension in spontaneously hypertensive rats (SHR). The present study was performed to determine if the antihypertensive effects of an antioxidant-rich diet are associated with reduction in the renal immune infiltration. Rats were divided into experimental groups (n=5 each) that were followed 7 months after birth, during which they were fed either a regular or antioxidant-enriched (test) diet as follows: SHR-R group=regular diet; SHR-T group=test diet throughout the experiment; SHR-S group=test diet for 4 months switched to regular diet thereafter; WKY group=control rats given regular diet. The SHR-T rats showed a significant reduction in systolic blood pressure (mm Hg): SHR-T=179.6+/-12.9 versus SHR-R=207.5+/-9.6 (P<0.001) and plasma hydrogen peroxide concentration (SHR-T=15+/-4 micro mol/L versus 34+/-9 in SHR-R rats). This was accompanied by significant reductions of renal tissue nitrotyrosine abundance, tubulointerstitial infiltration (cells/mm(2)) of lymphocytes (SHR-T=18+/-3 versus SHR-R=30+/-4, P<0.001), macrophages (SHR-T= 17+/-3 versus SHR-R=22+/-3), and angiotensin II-positive cells (SHR-T= 17+/-2 versus SHR-R=25+/-5, P<0.01). Results in the SHR-S group were intermediate between the SHR-R and SHR-T groups. The intensity of the infiltration of lymphocytes, macrophages, and angiotensin II-positive cells significantly correlated with systolic blood pressure. Thus, the present study demonstrates that an antioxidant-enriched diet reduces the renal interstitial inflammation and improves hypertension in SHR. These findings point to interrelation between oxidative stress and inflammatory reactivity in the pathogenesis of hypertension.

Animals↗
PubMed2002

Melatonin reduces renal interstitial inflammation and improves hypertension in spontaneously hypertensive rats.

Several studies have demonstrated that treatment with antioxidants improves hypertension in spontaneously hypertensive rats (SHR). Because our laboratory has shown that renal infiltration of immune cells plays a role in the development of hypertension (Rodriguez-Iturbe B, Quiroz Y, Nava M, Bonet L, Chavez M, Herrera-Acosta J, Johnson RJ, and Pons HA. Am J Physiol Renal Physiol 282: F191-F201, 2002), we did the present studies to define whether the antihypertensive effect of antioxidants was associated with an improvement in renal inflammation. Melatonin was administered as an antioxidant. For 6 wk, melatonin was added to the drinking water (10 mg/100 ml) given to a group of SHR (SHR-Mel; n = 10), and we compared them with groups of untreated SHR (n = 10) and Wistar-Kyoto (WKY) control rats (n = 10). Hypertension became increasingly severe in the SHR group [195 +/- 14.3 (SD) mmHg at the end of the experiment] and improved in the SHR-Mel group (149 +/- 20.4 mmHg, P < 0.001) in association with a 40-60% reduction in the renal infiltration of lymphocytes, macrophages, and angiotensin II-positive cells. Intracellular superoxide and renal malondialdehyde content were reduced by melatonin treatment as was the immunohistological expression of the 65-kDA DNA-binding subunit of NF-kappaB. We conclude that melatonin treatment ameliorates hypertension in SHR in association with a reduction in interstitial renal inflammation. Decreased activation of NF-kappaB, likely resulting from a reduction in local oxidative stress, may play a role in the suppression of renal immune infiltration and, thereby, in the antihypertensive effects of melatonin.

Administration, Oral↗
PubMed2002

Effect of mycophenolate mofetil on kallikrein expression in the kidney of 5/6 nephrectomized rats.

It has recently been proposed that tubulointerstitial damage plays a key role in the pathogenesis of sodium-dependent hypertension. Since components, enzymes and substrates, of the kallikrein-kinin system (KKS) are synthesized by connecting and collecting tubules, respectively, it is expected that damage of any origin, involving the tubulointerstitial compartment, may affect the functionality of these nephron segments and impair blood pressure control. Therefore, we analyzed renal kallikrein expression in the 5/6 renal ablation model, which is characterized by a progressive tubulointerstitial damage and systemic hypertension. In addition, we studied the renal expression of this enzyme after treatment of healthy and 5/6 nephrectomized rats with mycophenolate mofetil (MMF), an immunosuppressive drug known to reduce tubulointerstitial damage in this model. Twenty-six male Sprague-Dawley rats were included in this study. Seven 5/6 nephrectomized rats (Nx), 4 sham-operated (Sham) rats and 5 Nx rats treated with MMF (Nx + MMF) were studied 4 weeks after surgery. For comparison, 6 healthy rats treated with MMF at the same dose were compared with 4 vehicle-treated controls. Tubulointerstitial damage was significantly high in Nx compared with Nx-MMF and sham-operated rats. Blood pressure was significantly higher in Nx (178 +/- 7.8 mm Hg) than in Sham (120 +/- 2.0 mm Hg, p < 0.05) and Nx + MMF animals (154 +/- 5.6 mm Hg, p < 0.05). Renal kallikrein expression, quantified by a computer image system was significantly lower in the Nx group (1,696 +/- 437 density/mm(2)) than in Sham (9,779 +/- 4,068 density/mm(2), p < 0.05), and in Nx + MMF groups (4,640 +/- 1,578 density/mm(2), p < 0.05). Healthy animals treated with MMF did not show tubulointerstitial damage, changes in blood pressure nor changes in the expression of immunoreactive renal kallikrein suggesting that improvement in kallikrein expression after MMF treatment of 5/6 nephrectomy was not due to a direct effect of the drug on kallikrein-producing cells. Our results suggest that protection of the KKS after 5/6 nephrectomy may have additional renoprotective effects and may reduce the progression of renal disease.

Animals↗
PubMedDate not supplied

Hyperuricemia causes glomerular hypertrophy in the rat.

BACKGROUND/AIMS: Rats with mild hyperuricemia develop systemic hypertension, interstitial renal disease, afferent arteriolopathy, and increased renin expression [Mazzali et al.: Am J Physiol 2002;6:F991-F997]. We hypothesized that hyperuricemia might also induce glomerular changes. METHODS: We reviewed renal biopsies of rats previously made hyperuricemic for 7 weeks with the uricase inhibitor, oxonic acid. Controls included normal rats and oxonic acid-treated rats administered allopurinol, benziodarone, hydrochlorothiazide, or enalapril. Glomeruli were examined for size (computer image analysis) and structure (histology). An additional group of rats were administered oxonic acid or control diet for 6 months. RESULTS: Renal biopsies showed that hyperuricemic rats had a 30% increase in glomerular tuft area (p < 0.01); these changes were prevented by allopurinol and benziodarone. Control of blood pressure with hydrochlorothiazide did not prevent the development of glomerular hypertrophy, whereas enalapril partially reduced the glomerular hypertrophy. Prolonged hyperuricemia was associated with the development of microalbuminuria (p < 0.05) and glomerulosclerosis (22 vs. 10%, p < 0.05) compared to control rats. CONCLUSIONS: Hyperuricemic rats develop glomerular hypertrophy that can be prevented in part by ACE inhibitor therapy. Prolonged hyperuricemia is associated with the development of glomerulosclerosis in the rat.

Animals↗