The role of nitric oxide in experimental glomerulonephritis.

In recent years, nitric oxide (NO) has been identified as an effector molecule with multiple biological functions. NO production is physiologically involved in the regulation of vascular tone, platelet aggregation and hormone release, in neurotransmission, and in immune defense against several pathogens. However, uncontrolled up-regulation of NO release by cytokine-inducible NO synthases (iNOSs) may cause tissue damage in immune-mediated diseases.

L-arginine may mediate the therapeutic effects of low protein diets.

We have previously shown beneficial effects of dietary protein restriction on transforming growth factor beta (TGF-beta) expression and glomerular matrix accumulation in experimental glomerulonephritis. We hypothesized that these effects result from restriction of dietary L-arginine intake. Arginine is a precursor for three pathways, the products of which are involved in tissue injury and repair: nitric oxide, an effector molecule in inflammatory and immunological tissue injury; polyamines, which are required for DNA synthesis and cell growth; and proline, which is required for collagen production.

Nitric oxide mediates immunologic injury to kidney mesangium in experimental glomerulonephritis.

Background: Nitric oxide (NO), produced from L-arginine by an inducible NO synthase, is an important effector molecule in inflammatory and immunologic tissue injury. The role of NO generation in immunologic injury to glomerular mesangial cells and the effect of dietary restriction of L-arginine on this injury was investigated.

Experimental Design: Acute glomerulonephritis was induced by injection of anti-thymocyte serum (ATS) which binds to an antigen on the glomerular mesangial cell.

Transforming growth factor-beta and angiotensin II: the missing link from glomerular hyperfiltration to glomerulosclerosis?

Both angiotensin II and TGF-beta are key mediators of glomerular and tubulointerstitial injury and fibrosis in progressive kidney diseases. It was thought that angiotensin II damages the kidney by increasing glomerular filtration pressure, whereas autocrine TGF-beta overexpression occurs from unidentified mechanisms. Recent studies reveal that angiotensin II is a potent inducer of TGF-beta synthesis in a variety of cells and that this mechanism exerts important biological effects including extracellular matrix accumulation, cell proliferation, and hypertrophy.

Cytokines and L-arginine in renal injury and repair.

Advances in molecular biology have identified cytokines as mediators of pathophysiological changes in chronic renal disease. Transforming growth factor-beta (TGF-beta) plays an important role in the pathogenesis of glomerular and interstitial fibrosis, whereas platelet-derived growth factor (PDGF) is involved in proliferative changes in chronic progressive renal diseases. Tumor necrosis factor-alpha and interleukins are expressed in experimental models of renal disease and are causes of inflammation and cell migration.

Increased expression of transforming growth factor-beta in renal disease.

Transforming growth factor-beta (TGF-beta) is a multifunctional cytokine and a major regulator of tissue repair and extracellular matrix. Recent studies show that TGF-beta overexpression in experimental and human kidney diseases leads to progressive glomerular and tubulointerstitial scarring and renal failure. New evidence suggests that angiotensin-converting enzyme inhibitors and a low-protein diet may slow the progression of chronic kidney diseases in part by suppressing TGF-beta overexpression.

[Significance of hyponatremia in patients with oropharyngeal tumors].

We observed 29 patients with hyponatremia associated with oropharyngeal carcinoma. In 19/29 the hyponatremia was attributable to a decreased effective arterial blood volume whereas in the remainder (10/29) the presence of SIADH could be demonstrated. These etiologies of hyponatremia were best differentiated by the plasma urea concentration (less than 30 mg/dl in SIADH), urate concentration (less than 4,0 mg/dl in SIADH) and creatinine concentration (less than 0,9 mg/dl in SIADH).

[Kidney function in heart failure].

Congestive cardiac failure is a syndrome in which a decrease of cardiac output triggers a series of neuro-humoral compensatory mechanisms in part involving the kidney. In this response, dysfunction of atrial volume receptors as well as disturbances of the autonomic nervous system have recently been demonstrated and are held responsible for excessive stimulation of angiotensin II, followed by adverse regulatory effects. Renal hemodynamic compensation for heart failure primarily involves constriction of efferent arterioles thereby defending glomerular filtration.

Natriuretic factors and lithium clearance in patients with the syndrome of inappropriate antidiuretic hormone (SIADH).

Because the syndrome of inappropriate antidiuretic hormone (SIADH) is a state of disturbed body fluid volume regulation and altered sodium balance we sought to determine if recently described volume regulatory factors were stimulated in SIADH. We measured atrial natriuretic peptide (ANP), endogenous digitalis-like natriuretic factor (EDNF) and urinary free dopamine in SIADH (n = 27). We also determined fractional clearance of lithium (FCLi).

Ionic conductances of cultured principal cell epithelium of renal collecting duct.

The ionic conductive properties were studied of epithelia of collecting duct principal cells which had been grown in primary tissue culture from renal cortex/capsule explants. When pretreated with aldosterone (10(-6) mol/l) and bathed on either surface with isotonic HCO3(-)-free Ringer's solution, the transepithelial voltage, Vte, varied between -21 and -72 mV (apical surface negative) while the transepithelial resistance, Rte, ranged from 0.4 to 1.

Role of diuretics, hormonal derangements, and clinical setting of hyponatremia in medical patients.

Because hyponatremia is frequently associated with preceding diuretic treatment and unrestricted fluid intake--conditions which have not been addressed sufficiently in published literature--we studied the pathophysiology and the clinical setting of such hyponatremia in a large group of internal medicine patients. We observed: a) Of an initial 310 patients with chemical hyponatremia only 204 (64%) had an associated plasma hypoosmolality. Since a normal plasma osmolality excludes a disturbance of water metabolism only the 204 patients with hypoosmolar hyponatremia were included in the study.

The charted and the uncharted waters of hyponatremia.

It was observed that hyponatremia has been evaluated by many studies of patients and laboratory animals. In virtually all of these the presence of nonosmotic ADH has been shown, but several details of this relationship remain controversial at this time. The role of specific receptor areas for ADH stimulation requires further study, particularly in the hyponatremia of a decreased effective arterial blood volume.