Previous studies have shown that hypertension causes endothelial dysfunction. To study the influence of exogenous nitric oxide (NO) on endothelial dysfunction produced by hypertension, we administered a non-depressor dose of nipradilol to two-kidney, one clip renovascular hypertensive rats (2K1C). Sprague-Dawley rats underwent either sham surgery (G-l) or clipping of the left renal artery. From day seven, 2K1C were randomized into 3 groups, placebo treatment (G-2), nipradilol treament (G-3, ) and propranolol treatment (G-4). Urinary NO^-₂ +N0^-₃ (NOx) excretion (UNOxV) was measured 4 weeks after clipping, and then, acetylcholine (Ach), A23187, or sodium nitroprusside (SNP) -induced relaxation were measured in the aorta. Blood pressure was increased in G-2, G-3, and G-4 compared to G-1. UNOxV was lower in G-2, G-3, and G-4 compared to G-1, but UNOxV was higher in G-3 compared to G-2 and G-4. Although Ach or A23187-induced relaxation was significantly decreased in isolated artery from G-2, G-3, and G-4 compared with those from G-1. Ach- or A23187-induced relaxation was improved in G-3. SNP induced relaxation did not differ among the 4 groups. These results suggest that exogenous NO from nipradilol reduces the endothelial dysfunction caused by hypertension without changing the blood pressure.

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The periodic structure of 24 hour blood pressure variation (circadian rhythm of blood pressure by ambulatory blood pressure monitoring (ABPM)) in hypertensive CAPD patients was investigated by a new method of analysis based upon the maximum entropy method (MEM). In addition, this method allows the adequacy of antihypertensive therapies to be evaluated in such patients. The results were as follows; 1) The frequency of non-dipper type hypertension was 88 % (36/41 cases), and the remaining 12 (5/41) were dipper type hypertension patients. The rise in morning blood pressure (morning surge : MS) was noted in 64% of the former. 2) Night time systolic blood pressure (182 ± 22 mmHg, n=36) was higher in patients with nondipper type hypertension than in those with the dipper type (151 ± 17 mmHg, n = 5, p <0.01). 3) The standardized level of systolic blood pressure (SLSBP) calculated by MEM analysis in patients with non-dipper type hypertension (177 ± 7 mmHg) was comparable with that in those with dipper type hypertension (168 ± 13 mmHg, ns). 4) Treatment with longacting Ca antagonist alone significantly reduced both SLSBP and the area over the SLSBP from 188 ± 18 mmHg to 160± 7 mmHg (p <0.01, n= 8), and area over the SLSBP from 2, 735 ± 340 mmHg ⋅ hr to 1, 945 ± 298 mmHg ⋅ hr (p < 0.01, n= 8). 5) In addition to long-acting Ca antagonist, administration of α₁-blocker given at bed time was significantly efficacious in reducing the rise in morning blood pressure, MS. The present study using MEM analysis of ABPM suggests that the blood pressure profile of hypertensive CAPD patients is characterized by a non-dipper type dominance and a frequent morning surge. Furthermore, the combined therapy with longacting Ca antagonist and α₁-blocker was substantially effective both in reducing the overall blood pressure level, and in inhibiting the MS. This combined antihypertensive therapy may be potentially useful to prevent CAPD patients from the future development of cardiovascular complications.

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Aggravation of anemia in chronic renal failure patients by angiotensin-converting enzyme inhibitors (ACEIs) has been attributed to the inhibition of angiotensin II which facilitates erythropoietin (Epo) production. This study was aimed at evaluating whether ACEIs aggravate anemia in maintenance hemodialysis patients and to investigate the influence of ACE gene polymorphism on erythropoiesis in these patients. Ninety-one hemodialysis patients were divided into 2 groups, based on whether or not they were administered ACEIs, into the ACEI group (n=24) and the non-ACEI group (n=67), and comparisons were made of the doses of recombinant human Epo (rHuEpo) administered, the hematocrit (Hct) and the plasma Epo concentrations. Among the patients in the non-ACEI group, only 17 did not receive rHuEpo, while all of the patients in the ACEI group received rHuEpo. The average dose of rHuEpo was 102.7±45.4IU/kg/week in the ACEI group and 57.8±55IU/kg/week in the non ACEI group and the difference between the two groups was statistically significant. A statistically significant difference in the Hct was also observed between the two groups : the mean Hct in the ACEI group was 28.7±2.9 % while that in the non ACEI group was 31.1 ± 3.7 %. The plasma Epo concentrations were significantly lower in the ACEI group than in the non ACEI group. No significant differences in the rHuEpo dose and Hct were observed between the three ACE genotype classes in either the ACEI or the non ACEI group, however, there was a significant difference among the three genotypes in the non-ACEI group in regard to the plasma Epo concentrations ; patients with the DD genotype had higher concentrations than those with the DI or II genotypes. These data suggest that anemia in maintenance hemodialysis patients is worsened by ACEIs as a result of the suppression of Epo production. Although it has been suggested that the endogenous Epo concentra tions in maintenance hemodialysis patients are associated with ACE gene polymorphism, no significant influence of the ACE genotype on the rHuEpo dose or Hct was evident. Therefore, it is possible that exacerbation of anemia by ACEIs in the patients receiving rHuEpo is a result of an inhibited bone marrow response to Epo.

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We describe the clinical course of a 69-year-old woman, who suffered from minimal change nephrotic syndrome (MCNS) after long-term remission. In she was admitted to due to MCNS verified by renal biopsy and was treated with oral prednisolone (initially 40 mg/day) for two years. She suffered from edema again in with massive proteinuria. Renal biopsy revealed minor glomerular abnormality without any deposition of immunoglobulins or complements. Electron microscopic findings showed extensive foot process effacement. Therefore, we diagnosed this case as a recurrence of MCNS. She was treated with the combination of methylprednisolone pulse therapy (500 mg, 3 days), oral prednisolone (20 mg/day) and cyclosporin (CyA, 3 mg/kg/day), which could induce earlier complete remission. These results suggest that recurrence after long-term remission could occur in adult onset MCNS and that the combination therapy of prednisolone and CyA may be effective for the induction of early remission in MCNS.

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The association between selective serotonin reuptake inhibitors (SSRIs) and hyponatremia has been documented throughout the world. In Japan, since SSRIs have recently come into use for patients with depression, there are only a few reports of hyponatremia associated with SSRIs . We present here three cases of the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) associated with the administration of fluvoxamine for depression. They were admitted to our hospital because of deep coma, and revealed severe hyponatremia. Their serum sodium levels were 103-112 mEq/l, serum osmolalities were 227-241 mmol/kg, urine sodium levels were 38-l07 mEq/l, and urine osmolalities were 352-781 mmol/kg. These patients were started on fluvoxamine 3 days-3 months previously . The diagnosis of SIADH in these patients was made based on hyponatremia, and low serum and high urine osmolalities. The fluvoxamine treatment was discontinued, and hypertonic saline was infused . Their serum sodium levels and osmolalities were subsequently normalized . None of the other known causes of hyponatremia, including diuretic therapy, tumors, and respiratory and central nervous system diseases, were present. High plasma AVP levels observed in the two cases suggest that SSRIs stimulate AVP secretion, thereby causing SIADH. Many reports have shown that people older than 70 years were at a particularly high risk of developing hyponatremia when SSRIs were used. In the future, since the use of SSRIs will be increasing, the water and electrolyte balance of elderly patients should be monitored carefully during SSRIs therapy.

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