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Biomedical subjects

J L Ader

Publications and source records attributed to J L Ader.

At least 55 records · Page 3Linked to original sources

[Arterial hypertension with hyperkalemia, tubular acidosis and normal renal function: Gordon syndrome and/or pseudohypoaldosteronism type II?].

Basic examination of Mr S., 45 years of age, short in stature and overweight (1.60 m, 76 kg), was carried out because of the mild hypertension (mean AP 125 mm Hg) from which he had suffered for 20 years. The results were as follows: (1) variable hyperkalemia: plasma potassium values were 5.3 to 6.9 mmol/l; (2) normal renal function: serum creatinine 91.5 mumol/l, clearance of inulin 136.6 ml/mn; (3) proximal tubular acidosis: plasma bicarbonate and chloride values were 18.4 and 109 mmol/l, respectively; urinary pH was 7.1 with negative H+ ions urinary excretion (-33 mumol/mn); when plasma bicarbonate level was raised to 26 mmol/l by acute loading, fractional excretion of bicarbonate increased to 19,5 p. 100 while plasma potassium value decreased to 4.2 mmol/l; (4) low PRA (0.29 ng/ml/h) and normal plasma aldosterone concentration (63 pg/ml) with a normal intake of sodium and in a recumbent position. Plasma atrial natriuretic factor (ANF) level was normal: 14 fmol/ml. Intravenous infusion of ANF for 2 h (1 microgram/mn) induced the expected increases in urinary flow rate, and sodium and potassium excretions (+226, +307 and +171 p. 100, respectively). Intravenous infusion of isotonic saline (2 l in 2 h) and oral administration of fludrocortisone acetate for 4 weeks (400 micrograms per day) resulted in a normal decrease in PRA and plasma aldosterone concentration, a normal rise in plasma ANF level (22 and 42 fmol/ml) while slightly increasing AP without improving bicarbonaturia and acidosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Acidosis, Renal Tubular↗

Reduced urinary kallikrein activity in rats developing spontaneous hypertension.

Urinary kallikrein activity, intake, and excretion of sodium and water were measured in metabolic balance studies on spontaneously hypertensive rats (SHR) of the Okamoto-Aoki strain and normotensive Wistar-Kyoto rats (WKY) on a normal sodium diet from 4 through 15 wk of age. Urinary excretion of active and total kallikrein was significantly lower in SHR at all ages examined and represented a stable percentage of the values in age-matched WKY throughout development, on the average 69.5 and 67.4%, respectively. SHR exhibited a lower urinary excretion of sodium and water than WKY, a higher cumulative sodium balance at all ages studied, and a higher cumulative water balance only at ages 7 and 8 wk. The slopes of the regression lines correlating urinary kallikrein to systolic arterial pressure and to urinary excretion and cumulative balance of sodium and water were always significantly less in SHR than in WKY. The results of the present study indicate that SHR developing hypertension exhibit a precocious and stable abnormality in renal excretion of kallikrein activity.

Animals↗

Experimental and clinical approaches to treatment of hypertension by dopamine receptor agonists.

The action of several dopamine agonists on blood pressure was investigated. In dogs, apomorphine induced a decrease in blood pressure and an increase in heart rate. These effects were suppressed by intravenous haloperidol or phentolamine. Intravenous but not intracisternal domperidone suppressed the hypotensive responses elicited by intravenous or intracisternal apomorphine. Furthermore, the hypotensive effect of bromocriptine or apomorphine was abolished in adrenal demedullated dogs. Apomorphine and bromocriptine decreased adrenal catecholamine levels. In men, the acute hypotensive property of apomorphine (but not the long term effect of bromocriptine) was suppressed by pretreatment with domperidone. In hypertensive Parkinsonians, bromocriptine reduced blood pressure, induced an increase in inulin clearance, a decrease in plasma creatinine concentration and in renal vascular resistances. These results suggest that dopamine agonists (like apomorphine or bromocriptine) reduce blood pressure through both a decrease in sympathetic tone and an improvement in renal function. However, the mechanism of the acute and long term hypotensive effects could be different only involving peripheral mechanisms after acute administration and both peripheral and central structure under chronic treatment. In addition, preliminary results suggesting the potential interest of dopamine antagonists in the management of orthostatic hypotension are discussed.

Dopamine↗

[Metabolic balances of sodium and water in young spontaneously hypertensive rats and the effects of chronic inhibition of the conversion enzyme].

In order to show in SHR to what extent the kidneys excrete salt and water in proper relation to intake and whether antihypertensive action of converting enzyme inhibition (CEI) involves changes in salt--and water--balance, metabolic studies were conducted during 12 weeks following weaning (wk 4 to 15) on 4 groups of 9 male rats: SHR, WKY and SHR.C, WKY.C (C: given 30 mg captopril/kg body wt every 12 hr by gavage), all fed a standard rat chow (sodium 104 +/- 3 meq/g) in metabolic cages with free access to distilled water. SHR exhibited a higher weekly sodium retention than WKY only up to the end of wk 9 (5.2 +/- 0.5 vs 3.4 +/- 0.6 mEq/wk, p less than 0.001). This was due to lower urinary excretion and greater intakes since fecal losses were higher. From ages 10 through 15 wk, weekly sodium retention was the same in both strains although urinary sodium excretion in SHR was still significantly lower. SHR also retained more water at 7 and 8 wk than age-matched WKY due to lower urinary excretion. From ages 4 to 15 wk, SHR exhibited a reduced relationship of urinary sodium and water excretion to systolic arterial pressure. From ages 4 to 15 wk, weekly sodium retention in SHR.C (2.9 +/- 0.9 mEq/wk) was below that in SHR (4.5 +/- 0.9 mEq/wk, p less than 0.05) and not different from that in WKY (3.7 +/- 0.8 mEq/wk). As intakes and fecal losses were unchanged by CEI, this was due to increased urinary sodium excretion in SHR.C over that in SHR (by 1.4 +/- 0.5 mEq/wk.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗

Dissociation of urinary kallikrein activity and salt and water excretion in the rat.

Experiments were designed to examine the relationship, if any, between urinary kallikrein activity (amidolytic assay) and sodium and water excretion in 12-wk-old Munich-Wistar rats. Five groups of animals were studied: euvolemic, saline-expanded and water-loaded anesthetized rats, and euvolemic and saline-expanded conscious restrained rats. Following surgery, animals were allowed to stabilize (60-180 min) and reach a steady-state urine flow. By design, basal sodium and/or water excretion varied markedly among groups as a function of hydration state. Group means for sodium excretion and urine flow ranged from 0.8 to 12.4 mu eq/min and 6 to 112 microliter/min, respectively. In contrast, neither active nor total urinary kallikrein activity differed significantly among the five groups. In anesthetized euvolemic rats, intravenous administration of aprotinin produced a dose-dependent decrease in urinary kallikrein activity. The greatest inhibition of 93 +/- 3% (active) and 72 +/- 10% (total) was observed with a dose of 5,000 kallikrein inhibiting units (KIU)/kg and 1,000 KIU X kg-1 X min-1. This dose produced a significant decrease in active and total kallikrein activity in each group (P less than 0.001). However, sodium and water excretion were unchanged in aprotinin-treated rats and similar to values in vehicle-treated time-control groups. Linear regression analysis revealed no significant correlations between urinary kallikrein activity and sodium excretion or urine flow either among or within groups. These results indicate that urinary kallikrein activity is not related to acute sodium and water homeostasis in anesthetized or conscious rats.

Anesthesia↗

[Normalization of active urinary kallikrein excretion by young spontaneously hypertensive rats by chronic inhibition of conversion enzyme].

This study was designed to investigate the decreased urinary kallikrein excretion (Ukall.V) in Okamoto-Aoki spontaneously hypertensive rats (SHR) and the effect of long-term converting enzyme inhibition. From ages 4 to 7 weeks, Ukall.V was determined (amidolytic assay: nanokatals/wk) in 4 groups of 6 male rats housed into individual metabolic cages and fed a normal sodium diet: SHR and normotensive Wistar-Kyoto rats (WKY); SHR-C and WKY-C which were given captopril: 30 mg/kg BW every 12 hours by gavage. Ukall.V was each time lower in SHR than in age-matched WKY, even at 4 wks of age (54.6 +/- 9.1 vs 108.5 +/- 16.1 nkat/wk; p less than .01) when systolic blood pressure (s.BP) was already higher. In SHR-C, s.BP was identical or slightly lower to that in WKY. Ukall.V was still lower at wk 4 when captopril was first administered (60.9 +/- 8.4 nkat/wk; p less than .01), but identical to that in WKY at each subsequent age (105.7 +/- 25.9 vs 114.1 +/- 5.6 nkat/wk at wk 5; 219.8 +/- 44.5 vs 253.4 +/- 22.4 nkat/wk at wk 7). Excretion of active kallikrein was highly correlated to s.BP in WKY (r = .87), SHR (r = 0.91) and SHR-C (r = 0.95). The slope of the regression line relating Ukall.V with s.BP was significantly less in SHR than WKY (1.33 +/- 0.35 vs 3.36 +/- 0.84 nkat/wk/mmHg; p less than .01); the slope in SHR-C (3.35 +/- 0.77 nkat/wk/mmHg) was significantly steeper than in SHR (p less than .01) and identical to that in WKY.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Predictability of post-captopril acute renal failure in hypertension with renal artery stenosis of a single kidney or bilateral stenosis].

Use of converting-enzyme inhibitors in patients with hypertension and bilateral renal artery stenosis or renal artery stenosis in a single kidney may be complicated by acute renal failure (ARF). The aim of this work was to find a simple test to predict this accident. PAH clearance (CPAH), Inuline clearance (CIn) and Glomerular Filtration Fraction (GFF) were measured before and three hours after a single oral dose of Captopril (50 mg) in 7 hypertensive patients (sodium intake = 6 g/24 h). All these patients presented significant stenosis (greater than 60%) of the artery of a transplanted kidney (5), of a single kidney (1) or a bilateral renal artery stenosis (1). During the following three days, 50 mg captopril was given twice a day. ARF with creatinine serum level higher than 300 mumoles/l was seen in 4 patients (Group II); in 3 patients (Group I) creatinine serum level didn't change. Values measured before the single dose of captopril and variations after three hours are reported in the table: (Table: see text). Before captopril, in Group II CPAH and CIn are lower and GFF is higher, but these is not significant difference between the two groups. After Captopril CIn and GFF are significantly decreased in Group II (29.1 and 36.6% vs 7.8 and 10%). These results allow two conclusions: 1) Basal values of Glomerular Filtration Rate plasma flow and filtration fraction are not predictive parameters for acute renal failure after captopril therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗

[Decrease in urinary excretion of active kallikrein in conscious young and adult spontaneously hypertensive rats].

Urinary excretion of active kallikrein was determined every day (amidolytic assay) in 6 male Okamoto-Aoki spontaneously hypertensive rats (SHR) and 6 male normotensive Wistar-Kyoto rats (WKY) from ages 4 to 7 weeks and from 12 to 15 weeks. The rats were housed in individual metabolic cages and were allowed free access to food having normal sodium content and to tap water. Urinary kallikrein excretion was lower in 4-week-old SHR than in age-matched WKY (7.8 +/- 1.4 vs. 15.5 +/- 2.3 nkat/24 h respectively, P less than 0.01) at a moment when systolic blood pressure (BP) in SHR was already higher than in WKY. The slope of the increase in active kallikrein excretion from week 4 to 7 was not different for SHR and WKY (6.34 +/- 1.05 vs. 7.50 +/- 1.02 nkat/24 h-1 . wk-1 respectively). In contrast, from week 12 to 15, this slope was not significant for SHR (1.67 +/- 2.55 nkat/24 h-1 . wk-1) while it remained positive in WKY (7.36 +/- 3,44 nkat/24 h-1 . wk-1). In both SHR and WKY, urinary kallikrein excretion was directly related to BP from week 4 to 7 but the slope of the regression line was less for SHR than for WKY (0.19 +/- 0.05 vs. 0.48 +/- 0.12 nkat/24 h-1 . mm Hg respectively). From ages 12 to 15 weeks, kallikrein excretion was still related to pressure in WKY (y = 1.92 x - 180.8; r = 0.93) but not in SHR (y = 0.71 x - 81.48; r = 0.52).(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

Abnormalities in kallikrein excretion in spontaneously hypertensive rats.

Experiments were conducted to examine kallikrein excretion in 12-wk-old anesthetized and conscious Okamoto-Aoki spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). Urinary excretion of active and total kallikrein was determined at spontaneous pressures and in response to acute decreases in renal perfusion pressure (RPP; suprarenal aortic constriction). Under basal conditions, active kallikrein excretion was lower in SHR compared with WKY whether conscious (4.4 +/- 1.7 vs. 9.4 +/- 1.3 pkat . min-1 . g kidney wt-1) or anesthetized (5.7 +/- 1.3 vs. 10.4 +/- 1.7). In both anesthetized SHR and WKY, excretion of active and total kallikrein was directly related to RPP after 20 mmHg decrements in RPP and was depressed in SHR at each pressure level. The slope of the relation between active kallikrein excretion and pressure was less in SHR (0.06 +/- 0.01 vs. 0.14 +/- 0.05 pkat . min-1 . g kidney wt-1 . mmHg-1). Thus kallikrein excretion is set at a lower level in SHR and is less responsive to changes in RPP. These strain differences are not related to urine flow, Na excretion, or glomerular filtration rate (GFR) since the values were the same in both strains at each pressure level. Analysis of covariance indicated a significant correlation between active kallikrein excretion and RPP in WKY and SHR, with RPP accounting for 92% of the variation in the kallikrein data. GFR, Na excretion, and urine flow rate were not significantly correlated to active kallikrein and were responsible for only 2% of the variation.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, General↗

[Urinary kallikrein activity in conscious spontaneously-hypertensive rats: development as a function of age].

Urinary excretion of active kallikrein was determined every day (amidolytic assay) in 6 male Okamoto-Aoki spontaneously hypertensive rats (SHR) and in 6 male normotensive Wistar-Kyoto rats (WKY) from ages 3 to 6 weeks and from 12 to 16 weeks. The rats were placed into individual metabolic cages and allowed free access to food having normal sodium content and to tap water. Urinary kallikrein excretion (UKall V, nKat/24 h) was lower in 3-week-old SHR (7.8 +/- 1.4 nKat/24 h) than in WKY (15.5 +/- 2.3 nKat/24 h, p less than 0.01) at a moment when systolic blood pressure (BP) in SHR (85.5 +/- 4.0 mmHg) was already higher than in WKY (76.3 +/- 4.6 mmHg, p less than 0.01). The slope of the increase in kallikrein excretion from week 3 to week 6 was not different for SHR and WKY (y = 6.39 x - 12.09, r = 0.95 vs y = 7.49 x - 9.40, r = 0.93). In contrast, from week 12 to week 15, this slope was slightly negative for SHR (y = 1.08 x + 59.38, r = 0.66) and became significantly different (p less than 0.05) from the slope in WKY which remained positive (y = 5.09 x + 7.05, r = 0.48). The relation between kallikrein excretion and systolic BP was an exponential curve for both SHR and WKY. But the curve of SHR (y = 1.22.e0.03x, r = 0.91) was significantly different (p less than 0.01) from the curve of WKY (y = 1.08.e0.03x, r = 0.95). For each identical systolic BP, UKall V was always lower in SHR than in WKY.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

[Renal insufficiency after administration of captopril in renal artery stenosis with a single kidney or bilateral stenosis is not compulsory].

Acute renal failure has been reported during captopril therapy of hypertension due to renal artery stenosis with a single kidney or bilateral renal artery stenosis. Under low perfusion pressures inhibition of the renin-angiotensin system could disturb the autoregulation, decrease efferent arteriolar resistance and lead to a critical decrease in glomerular filtration. Renal function tests were repeated in a patient with hypertension due to 90 p. 100 renal artery stenosis with a single kidney, before and after captopril administration (sodium intake 100 mmol/24 h). (table; see text) Identical results have also been observed in a patient with bilateral renal artery stenosis. Both patients presented high risk renal haemodynamic states. The control of systemic blood pressure and the fall in filtration fraction were not associated with a critical, immediate or short term fall in glomerular filtration. The isolated administration of captopril is therefore not systematically contra-indicated in these two clinical situations.

Acute Kidney Injury↗

Bilateral urinary kallikrein excretion in the Goldblatt hypertensive rat.

Separate kallikrein excretions [RIA of generated Bradykinins (BK)] and renal functions were measured in 32 two-kidney, one-clip Goldblatt hypertensive (GH) and in 16 sham-operated (SO) rats either one, two, three or four weeks after operation. Mean blood pressure and plasma renin activity were higher in GH rats than in the respective controls. In GH rats, kallikrein excretion was lower from the clipped kidney than from the controlateral one (114 +/- 63 vs 220 +/- 87 ng BK min-1 per 30 min urine collection at week 1, P less than 0.05; 151 +/- 94 vs 425 +/- 125 ng BK min-1 per 30 min urine volume at week 4, P less than 0.01). While the excretion was normal from the controlateral kidney, GH rats had lower total kallikrein excretions than SO rats (335 +/- 138 vs 476 +/- 81 ng BK min-1 per 30 min urine volume at week 1, P less than 0.05; 556 +/- 179 vs 1078 +/- 191 ng BK min-1 per 30 min urine volume at week 4, P less than 0.01). Urinary kallikrein excretion is decreased in 2K-1C Goldblatt hypertension from one week to four weeks after clipping on account of an exclusive reduction in that from the stenotic kidney.

Animals↗

[Long-term treatment with captopril in arterial hypertension complicated by renal failure].

Twenty patients with severe hypertension and chronic renal failure were given Captopril during a one year period. Hypertension was always severe: BP: 193 +/- 11.8 mmHg/120.2 +/- 6.7 mm Hg. Mean glomerular filtration rate (GRF) was 42 +/- 10 ml/mn and renal plasma flow (RPF) was 160 +/- 35 ml/min. Mean plasma renin activity was 1.5 +/- 1.1 ng/ml/h and plasma aldosterone 15.9 +/- 1.9 ng/100 ml. Captopril was given in daily doses from 75 to 300 mg. Furosemide was added in 13 cases, and bêta inhibitions in 10 cases. Blood pressure and renal function were measured eight days, every month end after one year of treatment: the fall in diastolic blood pressure was 13 p. 100 after eight days, 23 p. 100 after one year; a period of at least 6 months was necessary to obtain normal blood pressure values; and after one year blood pressure was normalized (diastolic BP less than 90 mmHg) in 19 patients. Renal function was compared with pretreatment values, after 8 days and one year: --RPF was increased (+18 p. 100 and +10.3 p. 100); --GFR was unchanged (+3,8 p. 100 and -8.8 p. 100); --filtration fraction was significantly decreased: (-12.3 p. 100 and -18.3 p. 100); --sodium excretion rate (+16 p. 100 and +9.9 p. 100) and kaliemia increased (+10 p. 100 and +8 p. 100) but severe hyperkalemia never occurred; --PRA increased (+270 p. 100 and +400 p. 100); --Plasma aldosterone was decreased after eight days --28.9 p. 100 but identical to control after one year -4.4 p. 100. Diuretics were efficient to enhance the antipressor of Captopril, whereas bêta inhibitions appeared less useful, and may be indicated only when tachycardia occurs. These results show that long term use of Captopril alone or associated with Furosemide, can normalise blood pressure in patients with renal insufficiency, without any impairment in GFR, and with an increase in RBF.

Adrenergic beta-Antagonists↗

[A technique of transposed dog kidney perfusion at steady pressure (author's transl)].

One limitation of the technique of isolated dog kidney perfusion with heparinized blood is the progressive impairment of the organ function which leads to perfuse separately and simultaneously the two kidneys of the same animal with two identical apparatuses, one of the kidneys being used as a control. In order to overcome this difficulty, we describe a technique of perfusion where the kidney is transposed to the femoral or the carotido-jugular vessels. Interposition of a reservoir and a ventricular pump between the vessels and the kidney secures perfusion at a steady pressure. In 10 experiments, haemodynamics and functions of the kidneys remained steady and nearly normal during a 150 min perfusion.

Animals↗