Angiotensin II binding sites in individual segments of the rat nephron.

Mujais, Salim; Kauffman, S; Katz, Adrian I.

doi:10.1172/jci112293

Cited by 125 publications

(58 citation statements)

References 19 publications

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“…The decrease in mRNA for ACE and AT1AR in I/R injury cannot be explained merely by the loss of the proximal tubular cells, which is the major site for ACE and AT1AR gene expression in the kidney (47,48), because, even in the WT mice subjected to I/R, where there is little morphological change in proximal tubules, the expression of ACE and AT1AR was substantially decreased. Given the well documented ability of angiotensin II to stimulate reactive oxygen species and to cause TGF-␤1 production, the down-regulation of the renin-angiotensin system in I/R injury may be protective.…”

Section: Discussionmentioning

confidence: 99%

Bradykinin B1 and B2 receptors both have protective roles in renal ischemia/reperfusion injury

Kakoki

McGarrah

Kim

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

120

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To explore the role of the kallikrein-kinin system in relation to ischemia/reperfusion injury in the kidney, we generated mice lacking both the bradykinin B1 and B2 receptor genes (B1RB2R-null, Bdkrb1 ؊/ ؊/Bdkrb2 ؊/؊ ) by deleting the genomic region encoding the two receptors. In 4-month-old mice, blood pressures were not significantly different among B1RB2R-null, B2R-null (Bdkrb2 ؊/؊ ), and WT mice. After 30 min of bilateral renal artery occlusion and 24 h of reperfusion, mortality rates, renal histological and functional changes, 8-hydroxy-2 -deoxyguanosine levels in total DNA, mtDNA deletions, and the number of TUNEL-positive cells in the kidneys increased progressively in the following order (from lowest to highest): WT, B2R-null, and B1RB2R-null mice. Increases in mRNA levels of TGF-␤1, connective tissue growth factor, and endothelin-1 after ischemia/reperfusion injury were also exaggerated in the same order (from lowest to highest): WT, B2R-null, and B1RB2R-null. Thus, both the B1 and B2 bradykinin receptors play an important role in reducing DNA damage, apoptosis, morphological and functional kidney changes, and mortality during renal ischemia/reperfusion injury.hypoxia ͉ mitochondria ͉ oxidative stress I schemic tissue injuries, including stroke, myocardial infarction, and ischemic acute renal failure, are devastating complications in patients with hypertension, diabetes, atherosclerosis, and senescence. In organ transplantation, damage to allografts during any ischemic period before the transplant markedly influences short-term and long-term graft function and outcome (1). Furthermore, although reoxygenation after ischemia is essential for cell survival, damage also develops during the reperfusion period. Previous studies have shown that acute ATP depletion, intracellular Ca 2ϩ accumulation, and increased generation of reactive oxygen species by mitochondria all play important roles in the pathogenesis of ischemia/reperfusion (I/R) injury (2).Angiotensin-I-converting enzyme (ACE) inhibitors (ACEIs) reduce not only chronic cardiovascular remodeling after ischemia but also acute tissue injury caused by I/R in the heart (3), lung (4), liver (5), and kidneys (6, 7). Several observations indicate that the beneficial effects of ACEIs in the acute phase are mainly due to activation of the bradykinin nitric oxide (NO) cascade as a result of inhibition of the inactivation of bradykinin, rather than due to suppression of angiotensin II formation. Thus, ACEIs are much more effective than angiotensin type I receptor antagonists in protecting against I/R (8-10), and bradykinin B2 receptor (B2R) antagonists and NO synthase blockers markedly attenuate the protective effects of ACEIs (8, 9, 11).Bradykinin and lysyl-bradykinin (kallidin) are generated from kininogens by the kallikreins and some other serine proteases. ACE, which is a carboxydipeptidase, inactivates both peptides by removing two amino acids from their carboxyl termini. In mammals, at least two receptors have been identified: the bradykinin B1 receptor (B...

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Section: Discussionmentioning

confidence: 99%

Bradykinin B1 and B2 receptors both have protective roles in renal ischemia/reperfusion injury

Kakoki

McGarrah

Kim

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

120

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“…It is increasingly recognized, however, that AII also directly affects renal epithelia. AT1R is present throughout the nephron (40), and signaling increases activities of the sodium hydrogen exchanger 3 in the proximal tubule, NKCC2 in the TAL, NCC of the DCT, and ENaC in the CNT and CD (41)(42)(43)(44). AII also regulates phosphorylation and activity of MR in renal intercalated cells, allowing induction of a transcellular Cl − reabsorption pathway (14).…”

Section: Discussionmentioning

confidence: 99%

Angiotensin II signaling via protein kinase C phosphorylates Kelch-like 3, preventing WNK4 degradation

Shibata

Arroyo

Castañeda‐Bueno

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

102

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Hypertension contributes to the global burden of cardiovascular disease. Increased dietary K + reduces blood pressure; however, the mechanism has been obscure. Human genetic studies have suggested that the mechanism is an obligatory inverse relationship between renal salt reabsorption and K + secretion. Mutations in the kinases with-no-lysine 4 (WNK4) or WNK1, or in either Cullin 3 (CUL3) or Kelch-like 3 (KLHL3)-components of an E3 ubiquitin ligase complex that targets WNKs for degradation-cause constitutively increased renal salt reabsorption and impaired K + secretion, resulting in hypertension and hyperkalemia. The normal mechanisms that regulate the activity of this ubiquitin ligase and levels of WNKs have been unknown. We posited that missense mutations in KLHL3 that impair binding of WNK4 might represent a phenocopy of the normal physiologic response to volume depletion in which salt reabsorption is maximized. We show that KLHL3 is phosphorylated at serine 433 in the Kelch domain (a site frequently mutated in hypertension with hyperkalemia) by protein kinase C in cultured cells and that this phosphorylation prevents WNK4 binding and degradation. This phosphorylation can be induced by angiotensin II (AII) signaling. Consistent with these in vitro observations, AII administration to mice, even in the absence of volume depletion, induces renal KLHL3 S433 phosphorylation and increased levels of both WNK4 and the NaCl cotransporter. Thus, AII, which is selectively induced in volume depletion, provides the signal that prevents CUL3/KLHL3-mediated degradation of WNK4, directing the kidney to maximize renal salt reabsorption while inhibiting K + secretion in the setting of volume depletion.renin-angiotensin-aldosterone system | distal tubule | hypertension | posttranslational modification | PHAII H ypertension affects 1 billion people worldwide and is a major risk factor for death from stroke, myocardial infarction, and congestive heart failure. The study of Mendelian forms of hypertension has demonstrated the key role of increased renal salt reabsorption in disease pathogenesis (1-4). Observational and intervention trials (5, 6) also indicate that increased dietary K + lowers blood pressure; however, the mechanism of this effect has been unclear.Pseudohypoaldosteronism type II (PHAII; Online Mendelian Inheritance in Man no. 145260), featuring hypertension and hyperkalemia, has revealed a previously unrecognized mechanism that regulates the balance between renal salt reabsorption and K + secretion in response to aldosterone (7). Aldosterone is produced by the adrenal glomerulosa in volume depletion, in response to angiotensin II (AII), and in hyperkalemia via membrane depolarization (8). In volume depletion, aldosterone maximizes renal salt reabsorption, whereas in hyperkalemia, aldosterone promotes maximal renal K + secretion. Volume depletion increases both the NaCl cotransporter (NCC) (9) and electrogenic Na + reabsorption via the epithelial Na + channel (ENaC) (10). The lumen-negative potential produced by ENa...

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“…In the jejunum, angiotensin II increases solute transport indirectly: angiotensin II potentiates sympathetic nerve activity and release of norepinephrine, which then changes epithelial cell transport via a, receptors (1). Proximal tubule cells are richly innervated (6,9,10), but they also have angiotensin II receptors (5,(11)(12)(13)(14). However, receptor-mediated stimulation of epithelial cell hydrogen ion secretion by angiotensin II has not been previously described.…”

Section: Introductionmentioning

confidence: 99%

Angiotensin II stimulation of hydrogen ion secretion in the rat early proximal tubule. Modes of action, mechanism, and kinetics.

Fu-ying¹,

Cogan²

1988

J. Clin. Invest.

185

100

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Angiotensin II binding sites in individual segments of the rat nephron.

Cited by 125 publications

References 19 publications

Bradykinin B1 and B2 receptors both have protective roles in renal ischemia/reperfusion injury

Bradykinin B1 and B2 receptors both have protective roles in renal ischemia/reperfusion injury

Angiotensin II signaling via protein kinase C phosphorylates Kelch-like 3, preventing WNK4 degradation

Angiotensin II stimulation of hydrogen ion secretion in the rat early proximal tubule. Modes of action, mechanism, and kinetics.

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