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Am J Physiol Renal Physiol 298: F177-F186, 2010. First published October 28, 2009; doi:10.1152/ajprenal.00464.2009.--Angiotensin II (ANG II) stimulates proximal tubule (PT) sodium and water reabsorption. We showed that treating rats acutely with the angiotensin-converting enzyme inhibitor captopril decreases PT salt and water reabsorption and provokes rapid redistribution of the [Na.sup.+]/[H.sup.+] exchanger isoform 3 (NHE3), [Na.sup.+]/Pi cotransporter 2 (NaPi2), and associated proteins out of the microvilli. The aim of the present study was to determine whether acute ANG II infusion increases the abundance of PT NHE3, NaPi2, and associated proteins in the microvilli available for reabsorbing NaCl. Male Sprague-Dawley rats were infused with a dose of captopril (12 [micro]g/min for 20 min) that increased PT flow rate ~20% with no change in blood pressure (BP) or glomerular filtration rate (GFR). When ANG II (20 ng x [kg.sup.-1] x [min.sup.-1] for 20 min) was added to the captopril infusate, PT volume flow rate returned to baseline without changing BP or GFR. After captopril, NHE3 was localized to the base of the microvilli and NaPi2 to subapical cytoplasmic vesicles; after 20 min ANG II, both NHE3 and NaPi2 redistributed into the microvilli, assayed by confocal microscopy and density gradient fractionation. Additional PT proteins that redistributed into low-density microvilli-enriched membranes in response to ANG n included myosin VI, DPPIV, NHERF-1, ezrin, megalin, vacuolar [H.sup.+]-ATPase, aminopeptidase N, and clathrin. In summary, in response to 20 min ANG II in the absence of a change in BP or GFR, multiple proteins traffic into the PT brush-border microvilli where they likely contribute to the rapid increase in PT salt and water reabsorption. hypertension; captopril

OBJECTIVE. To study whether pretreatment of newborn lungs by captopril inhibits meconium-induced lung injury and inflammatory cytokine expression. DESIGN. Four groups of 2-week-old rabbit pups were used for the study: group I, saline instilled rabbits; group 2, captopril-pretreated rabbits; group 3, meconium-instilled rabbits; and group 4, captopril-pretreated and then meconium-instilled rabbits. Each group was studied at different time points: 0, 2, 4, 8, and 24 hours after instillation of meconium. Experiments were done at the University of Illinois and Michael Reese Hospital at Chicago. After treatment and instillation of meconium, the right lung was fixed with formalin, and 2-[micro]m slices were obtained for immunohistochemistry. The left lung was used for obtaining of lung lavage and measurement of total proteins (for enzyme-linked immunosorbent assay) and mRNA (for reverse transcription-polymerase chain reaction) purification. RESULTS. We found that meconium induces inflammatory cytokine expression and apoptotic lung cell death. In situ end labeling revealed a dramatic DNA fragmentation in the meconium group, which supports the presence of apoptosis. Using enzyme-linked immunosorbent assay, we demonstrated increase of interleukin 6 and interleukin 8 cytokines in meconium-instilled lungs, which were significantly decreased in captopril-pretreated lungs. Captopril pretreatment also decreased meconium-induced cell death and angiotensinogen expression. We believe this effect is explained by the ability of captopril to decrease processing of ANGEN to angiotensinogen (ANG) I and finally to ANG II. It suggests that captopril inhibits ANG II-induced lung cell apoptosis. CONCLUSION. Our results demonstrate that captopril pretreatment significantly inhibits meconium-induced lung cell death, cytokine, and ANGEN expression in newborn lungs. Key Words meconium aspiration syndrome, captopril, apoptosis, newborn lungs, cytokines, Abbreviations MAS--meconium aspiration syndrome ACE--angiotensin-converting enzyme RT--reverse transcription PCR--potymerase chain reaction ELBA--enzyme-linked immunosorbent assay ISEL--in situ end labeling EtBr--ethidium bromide TN--tumor necrosis factor IL--interleukin ALTHOUGH MECONIUM ASPIRATION syndrome (MAS) is [...]

Byline: L. S. Milner (1), M. Yuskiw (1), A. Sadeghi-Nejad (2), M. A. Linshaw (1) Keywords: Key wordsaProteinuria; Growth hormone; Captopril; Glomerulosclerosis Abstract: aDeveloping male Sprague-Dawley rats (125 g) with adriamycin (doxorubicin hydrochloride) nephrosis (AN) were treated with growth hormone (GH) which may induce hyperfiltration potentiating glomerulosclerosis. Since captopril (CAP) reduces hyperfiltration, we studied its effects in GH-treated rats with AN. After 41, 76, and 90 days of therapy, urine protein excretion was significantly (P&lt 0.05) reduced in GH-treated AN plus CAP compared with AN rats receiving GH alone. After 90 days, urine protein, creatinine ratio was significantly (P&lt 0.05) increased in GH-treated AN (95.2+-13.9) compared with untreated AN (64.8+-7.8) and GH-treated AN rats plus CAP (41.8+-8.8). The mean serum cholesterol level was significantly (P&lt 0.05) reduced in GH-treated AN rats receiving CAP compared with AN rats receiving GH alone and untreated AN controls. Histologically tubular dilation was significantly (P&lt 0.05) reduced in GH-treated AN rats plus CAP compared with AN rats receiving GH alone. Tubular atrophy and scarring were significantly (P&lt 0.05) increased in AN rats treated with GH compared with untreated AN rats, and normalized in GH-treated AN rats plus CAP. We conclude that CAP reduces the proteinuric response of GH in rats with AN and ameliorates tubular injury. Author Affiliation: (1) Division of Pediatric Nephrology, New England Medical Center, NEMC 201, 750 Washington Street, Boston, MA 02111, USA Fax: +1-617-636-8388, GB (2) Division of Pediatric Endocrinology, Tufts University School of Medicine, Boston, Massachusetts, USA, US Article note: Received: 5 March 1997 / Revised: 7 October 1998 / Accepted: 9 October 1998

Byline: William Wong (1), David Mauger (2) Keywords: Hypertension; Wilms tumor Abstract: Hypertension is commonly associated with Wilms tumor, but hypertension secondary to renin-secreting Wilms tumor is uncommon. We present an infant with severe hypertension and renin hypersecretion, which was resistant to multiple antihypertensive agents. Blood pressure was eventually controlled with a combination of captopril and losartan. Author Affiliation: (1) Department of Nephrology, Starship Children's Hospital, Grafton, Private Bag 92029, Auckland, New Zealand (2) Department of Hematology and Oncology, Starship Children's Hospital, Auckland, New Zealand Article History: Registration Date: 26/03/2004 Received Date: 19/06/2003 Accepted Date: 03/03/2004 Online Date: 06/05/2004

Role of the renin-angiotensin system in regulation and autoregulation of renal blood flow. Am J Physiol Regulatory Integrative Comp Physiol 279: R1017-R1024, 2000.--The role for ANG II in renal blood flow (RBF) autoregulation is unsettled. The present study was designed to test the effect of clamping plasma ANG II concentrations ([ANG III]) by simultaneous infusion of the angiotensin-converting enzyme inhibitor captopril and ANG II on RBF autoregulation in halothane-anesthetized Sprague-Dawley rats. Autoregulation was defined as the RBF response to acute changes in renal perfusion pressure (RPP). Regulation was defined as changes in RBF during long-lasting changes in RPP. The results showed that a prolonged reduction of RPP reset the lower limit of autoregulation from 85 [+ or -] 1 to 73 [+ or -] 2 mmHg (P [is less than] 0.05) and regulated RBF to a lower level. Reduction of RPP to just above the lower limit of autoregulation (88 mmHg) induced regulation of RBF to a lower level within 10 min. Clamping [ANG III] per se reset the lower limit of autoregulation to 62 [+ or -] 5 mmHg. In this case, reduction in RPP to 50 mmHg did not induce a downregulation of RBF. We conclude that ANG II plays an important role in the resetting of the autoregulation limits. The ability to regulate RBF to a new level as a response to changes in RPP also depends on changes in [ANG III. renal perfusion pressure; captopril; resetting

Cardiac interstitial bradykinin release during ischemia is enhanced by ischemic preconditioning. Am J Physiol Heart Circ Physiol 279: H116-H121, 2000.--Ischemic preconditioning is known to protect the myocardium from ischemia-reperfusion injury. We examined the transmural release of bradykinin during myocardial ischemia and the influence of ischemic preconditioning on bradykinin release during subsequent myocardial ischemia. Myocardial ischemia was induced by occlusion of the left anterior descending coronary artery in anesthetized cats. Cardiac microdialysis was performed by implantation and perfusion of dialysis probes in the epicardium and endocardium. In eight animals, bradykinin release was greater in the endocardium than in the epicardium (14.4 [+ or -] 2.8 vs. 7.3 [+ or -] 1.7 ng/ml, P [is less than] 0.05) during 30 min of ischemia. In seven animals subjected to preconditioning, myocardial bradykinin release was potentiated significantly from 2.4 [+ or -] 0.6 ng/ml during the control period to 23.1 [+ or -] 2.5 ng/ml during 30 min of myocardial ischemia compared with the non-preconditioning group (from 2.7 [+ or -] 0.6 to 13.4 [+ or -] 1.9 ng/ml, P [is less than] 0.05, n = 6). Thus this study provides further evidence that transmural gradients of bradykinin are produced during ischemia. The results also suggest that ischemic preconditioning enhances bradykinin release in the myocardial interstitial fluid during subsequent ischemia, which is likely one of the mechanisms of cardioprotection of ischemic preconditioning. cardiac microdialysis; angiotensin-converting enzyme inhibitors; captopril; kinin receptors; myocardium