Angiotensin II-induced hypertension in bradykinin B2 receptor knockout mice.

The present study was performed to examine the role of endogenous bradykinin (BK) in the development of angiotensin II (Ang II)-induced hypertension in mice. BK B2receptor knockout (B2R-/-) and wild-type (B2R+/+) mice (22to 26 g) were infused with either saline (SAL) or Ang II (40ng/min) via an osmotic minipump implanted intraperitoneally. On day 12after implantation, there was no difference in systolic blood pressure (SBP, tail-cuff plethysmography) between SAL/B2R+/+ and SAL/B2R-/- mice(128+/-5 versus 133+/-6 mm Hg, n=24/group). In contrast, SBP was higher on day 12 of infusion in Ang II/B2R-/- than in Ang II/B2R+/+ mice (173+/-6versus 156+/-5 mm Hg; P<0.05, n=27 and 28). Mean arterial pressure (MAP)was also higher in anesthetized Ang II/B2R-/- mice than in Ang II/B2R+/+mice (139+/-3 versus 124+/-3 mm Hg; P<0.05, n=16 and 14). Unlike Ang II, long-term norepinephrine (NE) infusion via an osmotic minipump (45ng/min) caused equivalent increases in SBP in B2R+/+ and B2R-/- mice measured on day 12 after implantation (151+/-4 versus 149+/-5 mm Hg, n=9and 8). MAP also did not differ on day 13 after implantation between NE/B2R+/+ and NE/B2R-/- mice (120+/-6 versus 122+/-4 mm Hg, n=9 and 8). There were no differences in glomerular filtration rate and urinary sodium excretion among the groups. However, renal plasma flow (RPF) was lower in Ang II/B2R-/- mice than in Ang II/B2R+/+ mice (2.34+/-0.06 versus 4.33+/-0.19 mL x min-1 x g-1; P<0.05). Acute inhibition of NO synthase (NOS)with nitro-L-arginine-methyl ester (0.5 microg x g-1 x min-1) in SAL/B2+/+ and SAL/B2-/- mice caused equal increases in MAP (142+/-1 versus 145+/-1 mmHg) and decreases in RPF (2.06+/-0.06 versus 2.12+/-0.15 mL x min-1 x g-1).However, short-term NOS inhibition caused a greater increase in MAP of Ang II/B2R+/+ mice than of Ang II/B2R-/- mice, such that MAP after NOS inhibition in Ang II/B2R+/+ approached that of Ang II/B2R-/- mice (156+/-2versus 159+/-2 mm Hg). These changes were associated with a decrease in RPF in Ang II/B2R+/+ mice to values similar to those of Ang II/B2R-/- mice before NOS inhibition (2.12+/-0.09 versus 2.34+/-0.06 mL x min-1 x g-1). These results demonstrate that the kallikrein-kinin system selectively buffers the vasoconstrictor activity of Ang II. Furthermore, the enhanced susceptibility of B2R-/- mice to Ang II-induced hypertension and renal vasoconstriction is likely due to an impaired ability to release NO by endogenous kinins.

[Role of the kidney in long-term regulation of blood pressure and the development of hypertension]. / Uloha ledvin v dlouhodobé regulaci krevního tlaku a rozvoji hypertenze.

Evidence about the crucial role of the kidney in the development and maintenance of the "essential" hypertension (i.e. hypertension which is accompanied with the absence of any pathological change in any of body organs) and in the regulation of "normal" blood pressure level (BP) has been accumulated. Blood pressure is expressed as a product of cardiac output (CO) and total peripheral resistance (TPR). TPR almost entirely depends on the volume of the extracellular fluid (ECFV): With increasing volume BP rises and vice versa. ECFV--due to intensive maintenance of the osmolality--almost entirely depends on the total amount of sodium in the organism. This amount is not determined by the intake of salt, which is in every civilized population always higher than necessary. Sodium balance is therefore critically determined by the output of sodium, which is carried out almost entirely by the kidney. The output depends on the quantity of the glomerular filtration and on the tubular reabsorption. Under normal circumstances, the increased sodium intake is accompanied by an increased excretion via the mechanism called "pressure natriuresis". It is based on the prompt increase of sodium excretion after an increase of BP, resulting from the increased sodium intake. Mechanism of such elevated excretion is not clear; lot of evidence has been accumulated for the existence of a humoral principle produced within the kidney. Such assumption is supported by experiments in which a kidney is transplanted from a hypertonic donor to a normotensive recipient: hypertension in the recipient develops. Similarly, kidney grafting from a normotensive animal corrects the hypertension in an originally hypertensive recipient. Important role of the renin-angiotensin (RAS) and nitric oxide (NO) systems is often stressed in this context. If kidney is unable to excrete the ingested amount of sodium at the normal BP, blood pressure must rise and the shift of the pressure-natriuresis curve to the right is the necessary consequence. If these conditions are long lasting, hypertension develops soon and becomes "fixed" by rebuilding the resistance arteries architecture.

Withdrawal of steroids from triple-drug therapy in kidney transplant patients.

BACKGROUND: In renal transplant patients with stable graft function, triple-drug immunosuppression may not be necessary, while withdrawal of steroids may eliminate side effects. The primary aim of this study was to assess the risk of rejection after steroid withdrawal. METHODS: A total of 88 patients with stable graft function and serum creatinine <160 micromol/l, treated with cyclosporin A, azathioprine and prednisone were randomized into group A (n=46) with a gradual prednisone reduction to zero in the course of 6 months, and group B (n=42) on triple-drug therapy without change. At the time of randomization, fine-needle aspiration biopsy (FNAB) was carried out in all of the patients. After stopping steroids, the patients were followed up for a period of 12 months. RESULTS: Four patients failed to complete steroid withdrawal, three due to rejection, and one due to leukopenia. The proportion of rejection in three patients in group A (6.6%) was not significantly different from rejection in two patients in group B (4.8%). The mean value of serum creatinine was not significantly different in both groups in the course of follow-up. A finding of some degree of immunological activity in FNAB was made in four patients in each group, but none of these patients developed rejection. Compared with group B, significant decreases in serum cholesterol and blood leukocytes were observed in group A. Prednisone withdrawal did not have any influence on hypertension and serum triglycerides. CONCLUSIONS: Gradual withdrawal of steroids is not associated with a higher risk for rejection and has a beneficial effect on serum total cholesterol levels. FNAB was not a useful tool for predicting rejection.

[Withdrawal of prednisone from a triple combination of immunosuppressive agents after kidney transplantation]. / Vysazení prednisonu z trojkombinace imunosupresiv u nemocných po transplantaci ledviny.

BACKGROUND: Triple-drug immunosuppression may not be necessary in a majority of stabilized patients over 1 year after kidney transplantation. In contrary steroid withdrawal may be beneficial for the patient by elimination of side-effects. The primary aim of this study was assessment of the risk of rejection after the prednisone withdrawal. METHODS AND RESULTS: 88 patients 1 year after the first renal transplantation with stable graft function and serum creatinine < 160 mumol/l treated with cyclosporine-A, azathioprine and prednisone were randomized into group A (n = 46) with a prednisone withdrawal and group B (n = 42) on triple-drug therapy without change. At the time of randomization, fine-needle biopsy was carried out in all of the patients. In group A, the dose of prednisone was gradually reduced to zero in the course of six months and the patients were followed up for the next 12 months. In the group B, patients on triple-drug therapy were followed for the corresponding period of time. 3 patients (6.6%) in group A, and 2 (4.8%) in group B experienced rejection (NS). Mean values of serum creatinine were in the course of follow-up in both groups without any statistical difference. Suspect immunological activity or proved immunological activity in aspiration biopsy was present in 4 patients in each group, but one of them rejected the graft. In comparison with group B, a significant decrease of cholesterol and leukocytes was observed in group A. Prednisone withdrawal had no influence on hypertension and triglyceride. CONCLUSIONS: Gradual withdrawal of steroids is not associated with higher risks of rejection and has a beneficial effect on cholesterol levels. Aspiration biopsy was of no use for the prediction of rejection.

[Pregnancy after kidney transplantation]. / Tehotenství po transplantaci ledviny.

In the period 1966-1997 renal allografting was performed in 1746 recipients, 244 of whom were women in fertile age. In 32 of them 45 pregnancies were registered. 29 of them (64%) resulted in abortion, which was spontaneous in 4 and medically advised in 25. There were 16 labours, 4 of them free of any complications; of the latter, hypertension was the most frequent one (8). Of the former, 13 were solved by caesarean section and 3 were vaginal deliveries. Of 15 live babies 7 were immature (one died 1.5 year later of renal failure due to microcystic kidneys). No unfavourable effect of pregnancy on prognosis and on long-term graft function was found.

[A single-center controlled clinical study with Sandimmune Neoral after kidney transplantation]. / Monocentrická kontrolovaná klinická studie se Sandimmunem Neoral u nemocných po transplantaci ledviny.

The authors compared in a controlled clinical study two groups of patients after a first renal transplantation treated by triple drug immunosuppressive therapy. In a group of 31 patients the triple combination comprised Sandimmune Neoral. In the control group there were 30 patients who received Sandimmune. No differences were found between the two groups as regards the effectiveness of this treatment and the authors did not confirm a lower incidence of rejections described in patients treated with Sandimmune Neoral. They confirmed, however, a lower interindividual variability of Cy-A levels assessed specifically in patients treated with Sandimmune Neoral.

Initial state, outcome, and autopsy findings in a series of 200 consecutive traumatic comas. A computerised analysis.

Based on 200 nonselected consecutive cases of primary traumatic coma a preliminary mathematical model--computed, multiple linear regression analysis--has been developed, which seems to be suitable for calculating the prognosis from some initial anamnestic and clinical data. It is to be expected that the analysis of greater material will help to establish an even better model, e.g. by a more detailed age subdivision and choice of more or other factors. It is the aim of this report to encourage further work in this field.