20-Hydroxyeicosatetraenoic acid antagonist attenuates the development of malignant hypertension and reverses it once established: a study in Cyp1a1-Ren-2 transgenic rats.

We hypothesized that vascular actions of 20-hydroxyeicosatetraenoic acid (20-HETE), the product of cytochrome P450 (CYP450)-dependent ω-hydroxylase, potentiate prohypertensive actions of angiotensin II (ANG II) in Cyp1a1-Ren-2 transgenic rats, a model of ANG II-dependent malignant hypertension. Therefore, we evaluated the antihypertensive effectiveness of 20-HETE receptor antagonist (AAA) in this model. Malignant hypertension was induced in Cyp1a1-Ren-2 transgenic rats by activation of the gene using indole-3-carbinol (I3C), a natural xenobiotic.

Inhibition of soluble epoxide hydrolase improves the impaired pressure-natriuresis relationship and attenuates the development of hypertension and hypertension-associated end-organ damage in Cyp1a1-Ren-2 transgenic rats.

Objective: In the present study, we compared the effects of treatment with the novel soluble epoxide hydrolase (sEH) inhibitor (c-AUCB) with those of the AT1 receptor antagonist losartan on blood pressure (BP), autoregulation of renal blood flow (RBF) and on glomerular filtration rate (GFR) and the pressure-natriuresis relationship in response to stepwise reduction in renal arterial pressure (RAP) in Cyp1a1-Ren-2 transgenic rats.

Methods: Hypertension was induced in Cyp1a1-Ren-2 rats through dietary administration for 11 days of the natural xenobiotic indole-3-carbinol (I3C) which activates the renin gene. Treatment with c-AUCB and losartan was started 48 h before initiating administration of the diet containing I3C.

Similar renoprotection after renin-angiotensin-dependent and -independent antihypertensive therapy in 5/6-nephrectomized Ren-2 transgenic rats: are there blood pressure-independent effects?

1. Hypertension plays a critical role in the progression of chronic kidney disease (CKD) to end-stage renal disease (ESRD), but it has also been postulated that antihypertensive drugs that block the renin-angiotensin system (RAS) show class-specific renoprotective actions beyond their blood pressure (BP)-lowering effects. 2.

Intrarenal cytochrome P-450 metabolites of arachidonic acid in the regulation of the nonclipped kidney function in two-kidney, one-clip Goldblatt hypertensive rats.

Objective: The contribution of epoxyeicosatrienoic acids (EETs) and 20-hydroxyeicosatetraenoic acid (20-HETE) as cytochrome P-450 metabolites of arachidonic acid in the regulation of the nonclipped kidney function in two-kidney, one-clip (2K1C) Goldblatt hypertensive rats was investigated during the phases of initial and stable hypertension, that is, 7 or 27 days after clipping, respectively.

Methods: Male Hannover Sprague-Dawley rats had the right renal artery clipped or underwent sham operation. Urinary excretion of EETs, their inactive metabolites dihydroxyeicosatrienoic acids and of 20-HETE was measured.

Endothelin receptor blockade does not affect blood pressure or angiotensin II levels in CYP1A1-Ren-2 transgenic rats with acutely induced hypertension.

We found previously that selective blockade of endothelin ETA receptors is superior to nonselective ET(A)/ET(B) in attenuating hypertension and survival rate in Ren-2 transgenic rats (TGR). In the present pilot study, we were interested in whether similar effects will be found in TGR with inducible malignant hypertension (iTGR; official strain name Cyp1A1-Ren-2rats), which were derived from the original Ren-2 transgenic rat strain. Studies were performed in three-month old male iTGR.

Pivotal role of angiotensin II receptor subtype 1A in the development of two-kidney, one-clip hypertension: study in angiotensin II receptor subtype 1A knockout mice.

Objective: The present study was performed to examine in two-kidney, one-clip (2K1C) Goldblatt hypertensive mice: first, the relative contribution of angiotensin II receptor subtypes 1A (AT(1A)) and 1B (AT(1B)); second, the role of angiotensin II type 2 (AT(2)) receptors in the development of hypertension in wild-type (AT(1A)+/+) and AT(1A) receptor knockout (AT(1A)-/-) mice; and third, the role of increased nitric oxide synthase activity in counteracting the hypertensinogenic action of angiotensin II in this model.

Methods: AT(1A)+/+ and AT(1A)-/- mice underwent clipping of one renal artery and were infused with either saline vehicle or selective AT(2) receptor agonist CGP-42112A (CGP). Blood pressure was monitored by radiotelemetry.

Late-onset endothelin receptor blockade in hypertensive heterozygous REN-2 transgenic rats.

Our previous studies in heterozygous Ren-2 transgenic rats (TGR) have shown that early treatment with selective endothelin (ET)(A) receptor blockade is superior to nonselective ET(A/B) receptor blockade. The aim of this study was to evaluate the role of the ET system in male heterozygous TGR with established hypertension (late-onset treatment). TGR and control Hannover Sprague-Dawley (HanSD) rats were fed a high-salt diet and were treated concomitantly with the nonselective ET(A/B) receptor blocker bosentan or the selective ET(A) receptor blocker atrasentan from day 52 of age on.

Effects of chronic cytochrome P-450 inhibition on the course of hypertension and end-organ damage in Ren-2 transgenic rats.

The aim of the present study was to evaluate the effects of inhibition of cytochrome P-450 (CYP) activity by 1-aminobenzotriazole (ABT) and by CoCl(2), first, on the development of hypertension when treatment was started in young male heterozygous Ren-2 transgenic rats (TGR) and, second, on blood pressure (BP) when treatment was started in adult TGR with established hypertension. Normotensive Hannover Sprague-Dawley (HanSD) rats served as controls. In addition, the renal cortical activities of omega-hydroxylase, the enzyme catalyzing the formation of 20-hydroxyeicosatetraenoic acid (20-HETE), and of epoxygenase, the enzyme responsible for epoxyeicosatrienoic acids (EETs) production, and urinary excretion of 20-HETE and EETs in TGR and HanSD rats were assessed.

AT1 receptor blockade is superior to conventional triple therapy in protecting against end-organ damage in Cyp1a1-Ren-2 transgenic rats with inducible hypertension.

Objective: In the present study we compared the effects of treatment with the AT1 receptor antagonist candesartan and of 'triple therapy' (hydralazine, hydrochlorothiazide, reserpine) on the course of blood pressure, cardiac hypertrophy and angiotensin II concentrations after induction of hypertension in transgenic rats with inducible expression of the mouse renin gene (Cyp1a1-Ren-2 rats).

Methods: Hypertension was induced in Cyp1a1-Ren-2 rats through dietary administration of the natural xenobiotic indole-3-carbinol (I3C, 0.3%) for 4 days.

Soluble adhesion molecules and cytokines in patients with myasthenia gravis treated by plasma exchange.

Plasma exchange (PE) is an effective therapeutic method used in patients with myasthenia gravis (MG) refractory to common therapy and/or with life-threatening respiratory complications. Except for acetylcholine receptor antibodies (AChRAbs), some other inflammatory mediators possibly activated in MG may also be removed during PE. Serum levels of soluble adhesion molecules (sICAM-1 and sVCAM-1), IL-6 and soluble receptors for IL-2 (sIL-2R), IL-6 (sIL-6R) and TNF alpha (sTNF-R II) were measured in 20 MG patients assigned to treatment with PE.

Outcomes of atherosclerotic renal artery stenosis managed without revascularization.

Objective: To determine how often patients with renal artery stenosis (RAS) managed without revascularization progress to accelerated hypertension and/or renal failure.

Patients And Methods: We examined the outcomes of 68 patients (mean +/- SEM age, 71.8 +/- 0.

Long term treatment of IgA nephropathy with cyclosporine A.

20-50% of patients with IgA nephropathy (IgAN) reach end-stage renal failure. Yet a standard treatment for those with progressive course and/or great proteinuria is lacking. We treated 6 patients with biopsy proven IgAN, proteinuria over 3.

[Plasma leptin levels in patients with kidney diseases of various etiologies].

Background: Leptin is a new hormone influencing food intake, energy expenditure and body weight. This protein is produced by adipocytes, exerts its effects on brain, endocrine pancreas and other organs by activating transmembrane receptors and is cleared from plasma mainly by the kidneys. The aim of our study was to compare plasma concentrations of leptin in our nephrological out-patients and controls.

[Pathophysiology of diabetic nephropathy].

The epidemic increase of diabetic nephropathy stimulated also the interest in pathophysiological mechanisms that lead to the development of the disease. The main interest is concentrated on the glycosylation of proteins and lipids, activation of intracellular enzyme cascades (protein kinase C, aldosoreductase) and the effect of vasoactive compounds (NO, prostanoids, angiotensin II) and growth factors. Cytokines are also of great importance.

[Relation between plasma levels of IGF-I, leptin and TNF-alpha in diabetics].

Background: TNF-alpha, IGF-I and leptin are agents which influence insulin resistance, they play probably a part in the pathogenesis of diabetic nephropathy and influence mutually their production. The objective of the submitted investigation was to assess whether there exist relations between their concentrations in the plasma of diabetic patients.

Methods And Results: The authors examined 37 patients aged 18-67 years from a diabetic clinic, 10 with normal albuminuria and normal renal function, 12 with microalbuminuria and 15 with macroalbuminuria and/or reduced renal function.

[Soluble adhesive molecules and cytokines in patients with myasthenia gravis treated with plasmapheresis].

Background: Plasma exchange (PE) is effective therapeutic method used in patients with myasthenia gravis (MG) refractory to common therapy and/or with life-threatening respiratory complications. Except from acetylcholine receptor antibodies (AChRAb) some other inflammatory mediators possibly activated in MG may be also removed during PE.

Methods And Results: Serum levels of soluble adhesion molecules (sICAM-1 and sVCAM-1), IL-6 and soluble receptors for IL-2 (sIL-2R), IL6 (sIL-6R) and TNF alpha (sTNF-R II) were measured in 20 patients (pts) with MG indicated to the treatment with PE.

[Soluble cytokinin receptors in renal vasculitis and lupus nephritis].

Background: Activation of various cytokines, e.g. TNF alpha, IL-1 and/or IL-6 may play important role in the pathogenesis of renal vasculitis and lupus nephritis (LN).

[Diabetic nephropathy].

Diabetic nephropathy is one of the microvascular complications of diabetes. Its incidence is decreasing in insulin dependent patients, but extremely increasing in non-insulin dependent patients in developed countries. The development of nephropathy in an individual patient cannot be predicted in spite of new information about genetics and pathophysiology of the disease.

[Clinical spectrum of the antiphospholipid syndrome].

Antiphospholipid syndrome (APS) is characterized by multiple arterial and venous thromboses, repeated spontaneous abortions and thrombocytopenia, together with the presence of antiphospholipid antibodies in serum. We present three patients, two men and a woman, at the age of 43, 24 and 23 years respectively. The younger man and the woman had secondary APS and systemic lupus erythematosus, the older man had primary APS.

[Long-term administration of cyclosporine A in patients with IgA nephropathy].

Background: IgA nephropathy is the most common glomerulonephritis all over the world and a considerable proportion of the patients reaches end-stage renal failure. Yet the standard treatment for the patients with progressive course and/or great proteinuria is currently lacking. All suggested treatment protocols, including short-term treatment with cyclosporine A had equivocal results.

[Thromboembolic complications in nephrotic syndrome].

Thromboembolic complications of nephrotic syndrome are very frequent. They can occur in the arterial or venous circulation. Venous thromboses are frequently asymptomatic and are manifested only by pulmonary embolism.

[Plasma volume in polycystic kidney disease].

Hypertension is a common and serious complication of autosomal dominant polycystic kidney disease (ADPKD), occurring early in the course of the disease. Disorders of tubular transport of sodium and increased plasma and blood volume (PV and BV), as a consequence, are thought to be involved in the pathogenesis of hypertension in ADPKD. In order to evaluate PV and BV in early stage of ADPKD, PV and BV were measured with radioactive serum albumin dilution technique.

[Acute kidney failure associated with rhabdomyolysis].

The authors describe three cases of rhabdomyolysis and acute renal failure. In all patients rhabdomyolysis developed in conjunction with ingestion of alcohol, in two moreover in combination with compression of an extremity by body weight during prolonged immobility. One patient was hospitalized on the day when rhabdomyolysis developed, the second one more than 24 hours after and the third one only several days after development of the condition.

[Rhabdomyolysis and acute renal failure].

Rhabdomyolysis is damage of the skeletal muscles due to different causes which leads to the release of the contents of muscle cells into the blood stream and conversely to the penetration of water and other substances into muscles via the damaged membrane. This initiates many processes which damage the organism: hypovolaemia, hypocalcaemia, hyperkalaemia, hyperuricaemia, disseminated intravascular coagulation, renal failure. Renal failure in particular is a frequent and very serious complication.