Effect of low dietary calcium intake on blood pressure and pressure natriuresis response in rats: a possible role of the renin-angiotensin system.

Dietary Ca is an important modulator of blood pressure in humans and rats. Since the kidney plays a key role in the pathogenesis of hypertension, the effects of a low Ca diet (0.01% Ca) on blood pressure and pressure natriuresis response were studied in normotensive 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 examined. In the low Ca diet group, systolic blood pressure measured by the tail-cuff method was significantly higher than in the normal Ca diet group (1,1% Ca) 1 week after the diet (1 13.0 +/- 7.1 vs. 105.0 +/- 9.5mmHg, p < 0.05). After 4 weeks, the hypertension was more pronounced. Low dietary Ca intake significantly inhibited the water and sodium excretory responses to acute elevation of renal perfusion pressure by tightening an infrarenal aortic constriction. Treatment with an inhibitor of angiotensin-converting enzyme, captopril (30 mg/kg/day), completely abolished the elevation of blood pressure and attenuated 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 was enhanced by 30% in the low Ca diet group and there was a significant difference in the pressor response between the two groups. These results suggest a possible involvement of the renin-angiotensin system in the development of hypertension and an inhibitory effect on the pressure natriuresis response caused by low dietary Ca intake, via an enhanced sensitivity to angiotensin II.

Antineutrophil cytoplasmic antibodies (ANCA)-associated crescentic glomerulonephritis and propylthiouracil therapy.

Cutaneous vasculitis is an uncommon complication of propylthiouracil therapy. Although its pathogenesis remains to be established, detection of antineutrophil cytoplasmic antibodies (ANCA) in association with this type of vasculitis has recently been described. We report here 2 patients who developed ANCA-associated crescentic glomerulonephritis without evidence of cutaneous vasculitis during propylthiouracil treatment of hyperthyroidism. Improvement of the renal function and the disappearance of ANCA were correlately found after discontinuation of propylthiouracil and by corticosteroid therapy in both patients.

[Effect of low calcium diet on blood pressure and pressure natriuresis response in rats: role of the renin-angiotensin system].

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, p < 0.05). 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.

[Role of endothelium-derived nitric oxide in mediating the natriuretic response to acute extracellular volume expansion].

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.

[Assessment of the distribution of renal cortical blood flow by contrast ultrasonography].

The importance of the distribution of intrarenal blood flow in the regulation of various renal functions, such as urine concentration and sodium excretion, has been well recognized. However, there have been no reliable methods to measure local flow in the kidney in vivo. The present study demonstrated the usefulness of contrast ultrasonography combined with injection of sonicated 5% albumin for assessment of the distribution of renal cortical blood flow in eleven mongrel dogs. The left kidney was displayed by tomographic echography, and microbubbles of sonicated albumin were injected into the abdominal aorta above the left renal artery. Video density time curves were generated and fitted to a time-intensity curve. Intrarenal infusion of acetylcholine (4.0 micrograms/kg/min) increased renal blood flow (RBF) from 2.5 +/- 0.3 to 4.6 +/- 1.0 ml/min/g kwt (p < 0.01), and norepinephrine (0.5 microgram/kg/min) decreased RBF from 2.5 +/- 0.3 to 1.2 +/- 0.5 ml/min/g kwt (p < 0.01). There were significant positive correlations between percent change in RBF and peak intensity and area under the curve, which were calculated with a time-intensity curve. Furthermore, the inner/outer renal cortex ratio of peak intensity significantly increased during acetylcholine infusion (0.72 +/- 0.11 vs 0.86 +/- 0.09; p < 0.01), whereas no significant change was observed during norepinephrine infusion. These results suggest that renal contrast ultrasonography may be useful for real-time assessment of the distribution of renal cortical blood flow in vivo.

[A case of an elderly SLE patient associated with acute renal failure].

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.

Doppler sonographic measurement of phasic renal artery blood flow velocity in patients with chronic glomerulonephritis.

The phasic arterial blood flow velocity at the renal hilus was measured by Doppler sonography in 25 healthy subjects and 78 patients with chronic glomerulonephritis. Doppler velocity waveform was analyzed to give peak systolic velocity (S), end-diastolic velocity (D), resistive index (RI), and pulsatility index (PI). Creatinine clearance correlated with S (r = 0.76), D (r = 0.80), RI (r = -0.74), and PI (r = -0.85). Color Doppler sonography facilitated the detection of blood flow and permitted the measurement of absolute blood flow velocity, which previously had been difficult to determine. These results suggest that renal arterial blood flow as detected by Doppler ultrasonography may be useful for noninvasive, direct, rapid, and simple evaluation of renal function, although various modifying factors also need to be considered.

Dopaminergic modulation of the pressure-natriuresis response in rats.

OBJECTIVE: The present study was carried out to examine the involvement of dopamine in the pressure-natriuresis phenomenon which has been postulated as a major regulator of extracellular fluid volume and thereby arterial pressure. DESIGN: Dopaminergic modulation of the pressure-natriuresis response was studied in the innervated and denervated rat kidney, to allow a distinction between the effects of neural and extraneural dopamine. METHODS: The pressure-natriuresis response was studied in anesthetized Sprague-Dawley rats, in which neural and hormonal influences on the kidney were fixed by denervating the kidney and by intravenous infusion of aldosterone, hydrocortisone, vasopressin and norepinephrine. The innervation to the kidney remained intact in some experiments with the selective dopamine-1 antagonist SCH 23390. Urinary excretion of dopamine during the pressure-natriuresis response was also examined in the innervated and denervated rat kidney. RESULTS: Although infusion of dopamine at a dose of 2 micrograms/kg per min had no effect on the pressure-natriuresis response in rats in which neural and hormonal influences on the kidney were fixed, the slopes of the relations between urine flow, sodium excretion and mean arterial pressure in rats given 10 micrograms/kg per min dopamine were significantly greater than those found in the control rats. Renal plasma flow increased significantly in the dopamine-treated rats whilst glomerular filtration rate did not differ between the control and dopamine-treated rats. The dopamine-induced increase in the slope of pressure-natriuresis relationship and renal plasma flow were completely blocked by 0.5 micrograms/kg per min SCH 23390. However, infusion of SCH 23390 alone at 0.5 micrograms/kg per min did not significantly alter the pressure-natriuresis response in rats with either denervated or innervated kidney. In addition, urinary excretion of dopamine derived from neither neural nor extraneural origins was altered in parallel with variations in mean arterial pressure. CONCLUSION: These results suggest that exogenous administration of dopamine may affect the pressure-natriuresis response by altering the magnitude of arterial pressure-induced changes in tubular sodium reabsorption, via an action of dopamine-1 receptors. However, endogenous dopamine does not appear to be capable of modulating the pressure-natriuresis response.

[Study of recombinant human erythropoietin treatment on the anemia of predialysis patients].

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.

Successful resection of pheochromocytoma in a hemodialysis patient.

A 45-year-old woman with a pheochromocytoma who had been on regular hemodialysis for 4 years and underwent successful surgery is described. Careful preoperative management, including the use of prazosin and weight control, was carried out to prevent severe intraoperative and postoperative cardiovascular complications. Prazosin was given at an initial dose of 0.5 mg/day, and the dosage was increased to 20 mg/day prior to surgery. The increase in intravascular volume led to a gain of 3 kg in body weight. No deterioration of the cardiovascular or respiratory function was caused by these maneuvers, and surgery was performed without significant complications except for a rapid rise of blood pressure during tumor resection. To our knowledge, only one similar case report could be found in the English literature.

Total and split renal function assessed by ultrasound Doppler techniques.

We evaluated total and split renal functions from the pattern for renal arterial blood flow detected by ultrasound Doppler in healthy subjects and patients with varying degrees of renal function and disorders other than renovascular hypertension or severe aortic valvular disease. A renal-time pulsed ultrasonic echo-Doppler device at 2.5 MHz was used with a translumbar approach. The ratio of peak diastolic (D) to systolic (S) velocity correlated well with both p-aminohippurate clearance and creatinine clearance. Acceleration time was correlated with the clearance of neither compound. To evaluate the clinical usefulness of ultrasound Doppler in the assessment of split renal function, we compared the D/S ratio with the renal function obtained by radionuclide methods for individuals. The split renal glomerular filtration rate, calculated by a method which makes use of the early renal uptake of 99mTc-diethylenetriam-inepentaacetic acid, correlated well with the D/S ratio. These results indicate that the ultrasonic measurement of renal arterial blood flow by the pulsed Doppler method should be useful for assessment of total and split renal functions.

[Evaluation of the changes in intracranial water, sodium, phosphorus metabolites and intracellular cerebral pH in rats with acute dilutional hyponatremia].

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)

[Hyponatremia in isolated deficiency of adrenocorticotropic hormone: role of a decrease in aldosterone secretion independent of antidiuretic hormone excess].

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.

[Angiotensin and prostaglandins in the pressure-natriuresis response in rats].

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)