Renal functional decline and glomerulotubular injury are arrested but not restored by release of unilateral ureteral obstruction (UUO).

Murine unilateral ureteral obstruction (UUO), a major model of progressive kidney disease, causes loss of proximal tubular mass and formation of atubular glomeruli. Adult C57BL/6 mice underwent a sham operation or reversible UUO under anesthesia. In group 1, kidneys were harvested after 7 days.

Type 2 diabetes mellitus in mice aggravates the renal impact of hemorrhagic shock.

The objectives of this study were to determine whether type 2 diabetic mice would exhibit a more severe renal impact of hemorrhagic shock (HS) based on a recently described model of acute kidney injury and to determine the impact of HS on renal responses to hypoxia. We induced HS or sham procedure in type 2 diabetic and obese db/db mice. Creatininemia, glomerular filtration rate, urine output, histologic injury score, and kidney inductible molecule 1 mRNA were used to investigate the renal impact of HS.

Bradykinin inhibits high glucose- and growth factor-induced collagen synthesis in mesangial cells through the B2-kinin receptor.

Mesangial matrix expansion is an early lesion leading to glomeruloclerosis and chronic renal diseases. A beneficial effect is achieved with angiotensin I-converting enzyme inhibitors (ACEI), which also favor bradykinin (BK) B2 receptor (B2R) activation. To define the underlying mechanism, we hypothesized that B2R activation could be a negative regulator of collagen synthesis in mesangial cells (MC).

Angiotensin II-induced hypertension regulates AT1 receptor subtypes and extracellular matrix turnover in mouse retinal pigment epithelium.

Accumulation of specific deposits and extracellular molecules under the retinal pigment epithelium (RPE) has been previously observed in eyes with age-related macular degeneration (AMD) and may play a role in the pathogenesis of AMD. Even though age is the major determinant for developing AMD, clinical studies have revealed hypertension (HTN) as another systemic risk factor. Angiotensin II (Ang II) is considered the most important hormone associated with HTN.

Pharmacological blockade of B2-kinin receptor reduces renal protective effect of angiotensin-converting enzyme inhibition in db/db mice model.

Diabetic nephropathy (DN) can be delayed by the use of angiotensin-converting enzyme inhibitors (ACEi). The mechanisms of ACEi renal protection are not univocal. To investigate the impact of bradykinin B(2) receptor (B2R) activation during ACE inhibition, type II diabetic mice (C57BLKS db/db) received for 20 wk: 1) ACEi (ramipril) alone, 2) ACEi + HOE-140 (a specific B2R antagonist), 3) HOE-140 alone, or 4) no treatment.

[New perspectives for bradykinin in nephroprotection].

Various diseases such as arterial hypertension, diabetes and obesity result in renal diseases which are often irreversible and resistant to currently available therapies. Beside the control of glycemia in diabetic patients, only the blockade of the renin-angiotensin system is effective in reducing the occurrence of glomerulosclerosis and its development towards terminal renal failure. Inhibition of this system is based on the use of angiotensin-1 converting enzyme inhibitors (ACEI) and angiotensin AT1 receptor antagonists.

ACE inhibitor reduces growth factor receptor expression and signaling but also albuminuria through B2-kinin glomerular receptor activation in diabetic rats.

Diabetic nephropathy (DN) is associated with increased oxidative stress, overexpression and activation of growth factor receptors, including those for transforming growth factor-beta1 (TGF-beta-RII), platelet-derived growth factor (PDGF-R), and insulin-like growth factor (IGF1-R). These pathways are believed to represent pathophysiological determinants of DN. Beyond perfect glycemic control, angiotensin-converting enzyme inhibitors (ACEI) are the most efficient treatment to delay glomerulosclerosis.

Decreased renal NO excretion and reduced glomerular tuft area in mice lacking the bradykinin B2 receptor.

Bradykinin B(2) receptor knockout mice (B(2)-/-) have been useful to study the role of bradykinin under pathological conditions. With the use of these mice, it was shown that bradykinin plays an important role in angiogenesis, heart failure, salt-induced hypertension, and kidney fibrosis. Data on the role of the bradykinin B(2) receptor under physiological conditions using these mice are controversial and scarce, because these mice have no typical phenotype.

Induction of functional bradykinin b(1)-receptors in normotensive rats and mice under chronic Angiotensin-converting enzyme inhibitor treatment.

Background: The physiological effects of ACE inhibitors may act in part through a kinin-dependent mechanism. We investigated the effect of chronic ACE-inhibitor treatment on functional kinin B(1)- and B(2)-receptor expression, which are the molecular entities responsible for the biological effects of kinins.

Methods And Results: Rats were subjected to different 6-week treatments using various mixtures of the following agents: ACE inhibitor, angiotensin AT(1)-receptor antagonist, and B(1)- and B(2)-receptor antagonists.

Bradykinin B(1) receptor-mediated changes in renal hemodynamics during endotoxin-induced inflammation.

Kinins have been shown to influence renal hemodynamics and function. Under physiologic conditions, most kinin effects involve bradykinin B(2) receptors, but bradykinin B(1) receptors are often induced during inflammation. The purpose of this study was to examine in vivo the effects of bradykinin B(1) receptor activation on renal hemodynamics under normal and inflammatory conditions.