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Dietary Ca is an important modulator of arterial blood pressure in humans and rats. Since the kidney plays a key role in the pathogenesis of hypertension, the effect of a low Ca diet (0.01%Ca) on blood pressure and pressure natriuresis response was studied in Sprague-Dawley rats. In addition, a possible role of the renin-angiotensin system in the development of hypertension and an altered pressure natriuresis response resulting from low dietary Ca intake was investigated. In the low Ca diet group, systolic blood pressure determined by the tail-cuff method was significantly higher than in the normal Ca diet group (1.1%Ca) 1 week after the diet (113.0 +/- 7.1 vs. 105.0 +/- 9.5 mmHg, p0.05). Furthermore, low dietary Ca treatment significantly inhibited the water and sodium excretory responses to acute elevation of renal perfusion pressure. Treatment with an inhibitor of angiotensin converting enzyme, captopril (30 mg/kg/day), attenuated both the development of hypertension and the reduced pressure natriuresis response observed in Ca-deficient rats. Although plasma renin activity was not different between the low and normal Ca diet groups after the 2-week dietary regimen, the pressor response to angiotensin II injection was significantly greater in the low Ca diet group. These results indicate a possible involvement of the renin-angiotensin system in the development of hypertension and the inhibitory effects of the pressure natriuresis response caused by low dietary Ca intake, via enhanced sensitivity to angiotensin II.

To determine the role of endothelium-derived nitric oxide (EDNO) in mediating the natriuretic response to acute extracellular volume expansion (ECVE) with isotonic saline (3% of body weight per hour), the diuretic and natriuretic responses to ECVE were studied in anesthetized Sprague-Dawley rats during the intravenous infusion of an EDNO synthesis inhibitor, NW-nitro-L-arginine methyl ester (L-NAME). Intravenous infusion of L-NAME at the dose of 5 micrograms/kg/min significantly inhibited the diuresis and natriuresis in response to ECVE by 58% and 67%, without altering arterial pressure, effective renal plasma flow, glomerular filtration rate and basal excretory function. This inhibitory effect of L-NAME on the diuretic and natriuretic responses to ECVE was attenuated by the infusion of the EDNO synthesis precursor, L-arginine (1mg/kg/min), but not by D-arginine. In addition, pretreatment with 0.3 mg/kg of the angiotensin II receptor antagonist, L-158,809, normalized the diuretic and natriuretic responses to ECVE in L-NAME-treated rats, suggesting an angiotensin-II-dependency of the reduced renal excretory response to ECVE during EDNO synthesis inhibition. Neither L-arginine nor L-158,809 alone significantly altered the renal excretory response to ECVE compared with vehicle-treated control rats. These results suggest that EDNO might play an important role in the regulation of sodium and water excretion during ECVE, and indicate a possible interaction between EDNO and angiotensin II on the renal excretory function.

It has been described that a rapid worsening in renal function is uncommon in the elderly patient with lupus nephritis. We report a case of a 76-year-old man with rapidly progressive lupus nephritis. On admission, laboratory studies revealed massive proteinuria, telescoped urine, thrombocytopenia and azotemia. Hypocomplementemia and the positive presence of anti-DNA antibody and lupus anticoagulant were also noted. Because of a rapid deterioration of renal function, he was started on a regimen of steroid pulse therapy and plasmapheresis. Serum levels of complements gradually increased after initiation of these treatments, and three weeks later, improvements of renal function and nephrotic syndrome were obtained. A renal biopsy specimen taken five months after admission showed diffuse membranous glomerulonephritis. In addition, we examined renal arterial blood flow with Doppler ultrasound, and significant improvements of the velocity and pulsatility were observed during recovery of the renal function.

We conducted a multiple-center joint study on the effects of recombinant human erythropoietin (rEPO) for predialysis patients. rEPO was intravenously administered to 42 predialysis patients (13 males and 29 females) with hematocrit (Ht) levels of less than 30%. The subjects were divided into group A (28 cases) in which rEPO was administered twice a week, and group B (14 cases) with rEPO administration once a week. The initial administration dosage was 6000IU/week. The Ht levels were 22.6 +/- 3.3% for group A and 23.2 +/- 2.7% for group B before the administration of rEPO, and increased to 31.0 +/- 4.0% and 27.7 +/- 3.7% respectively twelve weeks after initiating administration. The levels of effective improvement on anemia included 'markedly effective' in 17 cases (80.9%) and 'effective' in 2 cases (9.5%) in group A, and 'markedly effective' in 5 cases (41.7%) and 'effective' in 3 cases (25.0%) in group B. No significant change was seen in serum creatinine (Cr) levels during the study period. In the evaluation of renal function by reciprocal serum creatinine (1/Cr), a consistent tendency was not recognized; thus, suggesting that the rEPO administration had no effect on the renal function. No variation of blood pressure was seen. As far as side effects were concerned, headache and heavy headedness were recognized in four cases. There were, however, no cases in which the severity of the side effects dictated the discontinuation of the rEPO administration. In conclusion, rEPO was judged to be a safe and effective treatment for the anemia of predialysis patients.

Although most prominent among the clinical manifestations associated with hyponatremia are central nervous system (CNS) symptoms, the alterations in brain function remain poorly understood. In the present study, the alterations in intracellular cerebral pH and intracranial water, sodium and phosphorus metabolites content in rats with acute dilutional hyponatremia were examined by using an in vivo nuclear magnetic resonance (NMR) technique which noninvasively provides continuous informations on intracellular phenomena. Acute dilutional hyponatremia was induced on anesthetized male Sprague-Dawley rats by intraperitoneal injection of distilled water with an initial dose of 10 ml/100 g bw, followed by an additional dose of 5 ml/100 g bw 40 min later. Arterial blood sampling and NMR measurements were made before and every 60 min after the initial injection of distilled water. The treatment with distilled water resulted in dramatic falls in serum Na, Cl and osmolality at 60 min after water loading (Na; from 143.4 +/- 2.6 to 112.3 +/- 1.3 mmol/l, Cl; from 101.02 +/- 2.2 to 78.4 +/- 5.4 mmol/l, Osm; from 306.3 +/- 5.8 to 247.3 +/- 7.3 mOsm/kg H20). 1H-NMR imaging showed the accumulation of brain water as dilutional hyponatremia developed. Intracranial Na content measured by 23Na-NMR spectroscopy decreased significantly at 60 min after of water loading to about 70% of that observed under control condition. Since it has been demonstrated that solute extrusion from the brain with resultant reduction of brain swelling occurs within 60 min after the dilution, this result may be, at least in part, explained by this protective mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)

We report a case of 47-year-old woman with an isolated deficiency of adrenocorticotropic hormone. She was admitted complaining of fatigue and frequent loss of consciousness. The patient developed severe hyponatremia (100 mEq/l) after five days of the admission. Her plasma renin activity and plasma aldosterone concentration were low though she was dehydrated. After the treatment of dehydration, plasma osmolality was low but high plasma antidiuretic hormone (ADH) level sustained. Both high urinary sodium excretion and low urinary aldosterone excretion still remained after one month of replacement therapy with prednisolone. But, glomerular filtration rate and a response of urinary volume to acute water loading were normalized. These results suggested that severe hyponatremia of the patient was caused by an inappropriate secretion of ADH and suppression of renin-aldosterone system. We consider the suppression of renin-aldosterone system was partially independent of an inappropriate secretion of ADH.

The possible roles of angiotensin and prostaglandins as humoral mediators of the pressure-natriuresis response were studied in anesthetized Sprague-Dawley rats. Neural and other hormonal influences on the kidney were held constant by denervating the kidney and by maintaining fixed high plasma levels of aldosterone, corticosterone, vasopressin and norepinephrine by continuous intravenous infusion. Acute elevation of arterial pressure by tightening the ligature placed around the abdominal aorta below the renal artery produced marked increases in urine flow and sodium excretion with no detectable changes in renal blood flow or glomerular filtration rate. In rats undergoing a saline diuresis, the pressure-natriuresis response was markedly inhibited by intravenous infusion of angiotensin II at a rate of 10 ng/kg/min. Blockade of prostaglandin synthesis with indomethacin also reduced the pressure-natriuresis response in the presence of low-dose (2 ng/kg/min) of angiotensin II, but indomethacin alone did not affect significantly. On the other hand, in rats with hydropenia indomethacin alone significantly inhibited the sodium excretory response to changes in arterial pressure. This indomethacin-induced inhibitory effect on the pressure-natriuresis response was completely attenuated in rats treated with captopril. These results indicate that angiotensin II is a powerful modulator of the pressure-natriuresis response. In addition, it has been suggested that prostaglandins are also capable of modulating the response only in the presence of the renin-angiotensin system. However, neither angiotensin nor prostaglandins appears to be essential for the basic pressure-natriuresis phenomenon since the pressure-natriuresis response can occur during blockade of both the renin-angiotensin and prostaglandin systems.(ABSTRACT TRUNCATED AT 250 WORDS)