[Converting enzyme inhibitors in arterial hypertension].
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Aged↗
Biomedical subjects
A Mimran
Publications and source records attributed to A Mimran.
Effect of different calcium antagonists on transcapillary fluid shift.
Chronic treatment with dihydropyridines, and to a lesser extent other calcium antagonists, often results in peripheral edema without fluid retention. The possibility that calcium antagonists affect extracellular fluid volume partition was tested by comparing the effects of nicardipine (Nic), diltiazem (Dil) and Vehicle (Veh) on hematocrit and plasma protein concentration in anephric anesthetized rats. In response to a 45 min infusion of Nic (0.1 or 1 micrograms/kg/min) and Dil (10 or 100 micrograms/kg/min), blood pressure decreased by 4 or 21%, and 4 or 19%, respectively, whereas hematocrit increased only with both doses of Nic (5.3 +/- 0.2 and 5.5 +/- 0.2%). Plasma protein concentration also increased significantly, although slightly, in the Nic group. The possibility of protein extravasation was then assessed using Evans blue dye as a marker. The drug-induced extravasation of dyed albumin in skeletal and cardiac muscles, but not other organs, was significantly increased following Nic, as compared to Dil or Veh. These observations suggest that two structurally different calcium antagonists used at equihypotensive doses may exert different effects on extracellular fluid partition.
Animals↗
Effect of angiotensin converting enzyme inhibition on blood pressure and renal function during open heart surgery.
Activation of the renin-angiotensin system during open heart surgery may have consequences both beneficial in sustaining blood pressure and deleterious in compromising renal hemodynamics. The influence of short-term pretreatment with captopril on blood pressure and renal function was assessed double-blind versus placebo in 18 patients without pre-existing cardiac or renal failure, and undergoing coronary artery bypass. No difference in blood pressure and fluid requirement during the surgical period was observed between groups receiving captopril or placebo. Effective renal plasma flow and glomerular filtration rate decreased in the placebo group whereas they remained unaltered in the captopril group; during cardiopulmonary bypass, urinary excretion of sodium was greater in patients receiving captopril than those receiving placebo. These results suggest that captopril pretreatment does not compromise the control of blood pressure and renal function during open heart surgery; additional studies on the protective value of angiotensin-converting enzyme inhibitors are warranted in patients at higher risk for developing renal failure.
Angiotensin-Converting Enzyme Inhibitors↗
Diabetic nephropathy in normotensive patients.
Arterial pressure is within 'normal' limits in most diabetic patients with or without microalbuminuria and elevated in 70% of patients with overt diabetic nephropathy. An abnormal increase in the level of urinary excretion is a strong predictor of the subsequent development of overt diabetic nephropathy and ultimately renal insufficiency. Correction of hypertension is associated with a reduction in the rate of decline of the glomerular filtration rate in overt diabetic nephropathy. In patients with microalbuminuria, short-term studies have shown that angiotensin converting enzyme (ACE) inhibitors, in contrast with calcium antagonists, decrease urinary albumin excretion. Additional studies assessing the long-term effect of antihypertensive agents on the evolution of early diabetic nephropathy are needed. The superiority of ACE inhibitors over other antihypertensive agents in the treatment of overt or early diabetic nephropathy remains to be demonstrated. In addition to arterial pressure control, it is possible that optimal glycaemic control in addition to the modification of protein intake, dietary sodium and serum lipid profile may alter the course of diabetic nephropathy.
Animals↗
Role of atrial peptide in the acute natriuretic response to uninephrectomy.
Unilateral nephrectomy (UNX) is associated with an immediate natriuretic response of the remaining kidney. The role of atrial natriuretic peptide (ANP), as assessed by right atrial appendectomy (APX), was investigated in euvolemic anaesthetized rats. In sham APX rats, UNX resulted in a twofold increase in urinary sodium and potassium excretion (1.03 +/- 0.11 to 2.08 +/- 0.17 and 1.39 +/- 0.05 to 2.26 +/- 0.08 mueq/min, respectively) and a doubling of urinary excretion of guanosine 3',5'-cyclic monophosphate (cGMP). No significant change in glomerular filtration rate, renal plasma flow, and lithium clearance occurred in response to UNX. APX totally prevented the UNX-induced natriuresis and diuresis as well as the rise in urinary cGMP. Post-UNX plasma concentration of ANP was higher in sham-operated compared with APX rats (45 +/- 9 vs. 20 +/- 2 fmol/ml). In sham APX rats, UNX was associated with a transient (less than 15 min) rise in arterial pressure; in APX rats, this immediate increase in arterial pressure was of similar magnitude but of longer (greater than 30 min) duration. The observed stimulation of ANP release after UNX and the blunting of the natriuretic response to UNX by APX suggest that ANP may be an important mediator of the renal response to contralateral renal ablation.
Animals↗
[Renal function and aging].
Aging is associated with structural changes and modifications in renal function occurring as a consequence of a decrease in the number of functioning nephrons. Glomerular filtration decreases with age at a rate of 0.8 ml/min/year, starting at the fourth decade of life. In addition, renal adaptation to dietary sodium restriction as well as sodium loading are impaired during the aging process. Changes in renal tubular function include the regulation of potassium excretion resulting in a relatively high incidence of hyperkalemia, spontaneously or facilitated by treatments known to produce potassium retention. Practical consequences of renal aging, specially adaptation of doses of medications with preferential renal elimination, are analyzed.
Aged↗
Is renal transplantation useful for the understanding of the pathogenesis of hypertension?
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Animals↗
[Pre- and postoperative antihypertensive treatment with calcium antagonist in pheochromocytoma].
Medical preparation for pheochromocytoma surgery requires adrenergic blockade and restoration of euvolemia. Usually, this preoperative preparation consisted essentially of sequential and progressive adrenergic antagonism, alpha then beta blockade. This therapy is not easy to introduce and exposes to blood pressure collapses after tumor removal. By contrast, calcium channel blocking drugs like dihydropyridines offer efficacy and safety. Moreover, new intravenous (IV) agents (nicardipine, diltiazem) provide useful therapeutic tools to control, rapidly and with a dose-dependent effect, any undesired hemodynamic event during surgery. As a demonstration of this new therapeutic strategy for management of pheochromocytoma resection, we report here the cases of two patients who were exclusively treated with dihydropyridines. A 61 year-old woman and a 41 year-old man were scheduled for pheochromocytoma resection (left and right adrenal tumors, respectively). Both patients received dihydropyridines for preoperative preparation (nicardipine and nifedipine, respectively, 60 mg/day). This treatment allowed a good control of arterial blood pressure (BP) (from 210/110 to 170/90 and 180/100 to 140/80 mmHg, respectively) and was maintained up to the morning of the operative day. After patient installation on the operating-table, IV nicardipine infusion was started (2 mg/hour). Anesthesia consisted of high doses of fentanyl, flunitrazepam and vecuronium. Hemodynamic measurements (radial artery and Swan ganz catheters) allowed adjustment of nicardipine infusion rate to maintain peripheral arterial resistances under 1,000 dynes.s.cm-5, and adequate volume loading. A hypertensive crisis (270/130 mmHg) occurred at the time of the intubation in the first case but responded to higher infusion rate of nicardipine (5 mg/10 min).(ABSTRACT TRUNCATED AT 250 WORDS)
Adrenal Gland Neoplasms↗
[Comparison of pro-edematous effects of 2 calcium antagonists in bilaterally nephrectomized rats].
Chronic treatment with dihydropyridines and to a lesser extent other calcium antagonists often cause peripheral edema without fluid retention. To test the possibility that calcium antagonists affect extracellular fluid partition between plasma and interstitium, we compared the effects of a benzothiazepine derivate diltiazem, a dihydropyridine derivate nicardipine and vehicle in binephrectomized anesthetized rats by measuring changes in hematocrit and plasma protein concentration. Forty minutes infusion of low dose of nicardipine and diltiazem (0.1 and 10 micrograms/kg/min respectively) had no significant effect on blood pressure (-2 +/- 2 and -4 +/- 3% respectively); nicardipine increased hematocrit by 5.6 +/- 0.5% (p less than 0.05); while diltiazem had no significant effect as compared to the vehicle (+1.5 +/- 0.3 and +1.5 +/- 0.3% respectively). The calculated loss of plasma volume during nicardipine infusion was 9.2 +/- 0.8% as compared to 2.5 +/- 0.6% and 2.7 +/- 0.6% in rats receiving diltiazem and vehicle respectively. Infusion of higher doses of nicardipine and diltiazem (1 and 100 micrograms/kg/min respectively) decreased blood pressure by 21 +/- 2 and 19 +/- 2% while the changes in hematocrit were not different than those observed with with the lower doses (5.5 +/- 0.6 and 1.4 +/- 0.3% respectively). To document and localize an alteration in vascular leak of proteins induced by the drugs, albumin-bound Evans Blue (EB) extravasation was measured spectrophotometrically in different tissues after extraction by formamide. Nicardipine but not diltiazem increased vascular permeation of EB-albumin in skeletal and cardiac muscle. No change was observed in brain, liver, spleen as compared to rats receiving the vehicle.(ABSTRACT TRUNCATED AT 250 WORDS)
Albumins↗
[Myocardial morphological changes related to sodium intake in normotensive and hypertensive patients never treated before].
Several factors have been implicated in the pathogenesis of myocardial hypertrophy, and the role of sodium has recently been suggested. In the present study, we assessed the influence of dietary sodium on the degree of left ventricular hypertrophy (LVH) and LV structure in 30 normotensive (NT) subjects aged 34 +/- 11 years (mean +/- SD) and 50 patients (39 +/- 10 years) with mild essential hypertension EH (canal blood pressure 154 +/- 16/96 +/- 11 mmHg), who had never received antihypertensive drugs. Posterior wall thickness (PWT) and left ventricular mass (LVM) were measured by M-mode echocardiography and urinary sodium excretion (UNa, mmol/24h) was taken as an index of sodium intake. In NT and EH, LVM was directly correlated with UNa (r = 0.48 and 0.49; p less than 0.006 and 0.002, respectively). A stepwise multiple regression analysis confirmed that UNa was a determinant of LVM independently of sex, age, and body weight in the two groups. In NT the correlation with UNaV was the result of an increase of the end-diastolic diameter without change in PWT whilst in EH it was the consequence of an increase in wall thickness (R = 0.49, p less than 0.0001) without a modification of LV diameter. These results suggest that salt intake may be an important determinant of cardiac structural adaptation in both NT and EH subjects; however, only EH have a salt sensitive LV wall hypertrophy.
Adult↗
[Left ventricular mass and glomerular hyperfiltration in essential hypertension].
OBJECTIVE: to assess the early involvement to target organs in never treated essential hypertensives (HT). METHODS: effective renal plasma flow (ERPF, 131I-Hippurate) and glomerular filtration rate (GFR, 99mTc-DTPA) were estimated in 80 mild HT. Left ventricular mass (LVM, M-mode echocardiography), sodium intake (24h UNaV) and urinary kallikrein (Kall) were also measured. Hyperfiltering patients (HF, GFR = 155 +/- 3 ml/min: 1.73 m2, n = 21) were defined by comparison with age-matched normotensive. HF patients were pair-matched for age, sex and blood pressure level with normofiltering hypertensives (NF, GFR = 112 +/- 3, n = 21). RESULTS: are expressed as mean +/- sem [table: see text] CONCLUSION: These results suggest that a high Na intake is associated with hyperfiltration and higher LVMI in subjects with never treated essential hypertension of short duration.
Adult↗
[Suppression of the immediate pressive response to unilateral nephrectomy by atrial natriuretic peptide in the rat].
Unilateral nephrectomy (UNX) is associated with an immediate and transient increase in arterial pressure and in prompt natriuresis from the remaining kidney. The hypothesis that atrial natriuretic peptide (ANP) is involved in the acute adaptation to unilateral nephrectomy was tested in euvolemic anesthetized Sprague-Dawley rats. In a first series of experiments, an increase in circulating ir-ANP levels (from 23.5 +/- 3.6 to 66.3 +/- 12.8 fmol/ml; p less than 0.01) was found within 2 minutes following renal exclusion. In a second set of experiments, the ANP response was inhibited by performing a right atrial appendectomy, in order to eliminate the major source of ANP, or by intravenous administration of monoclonal antibodies directed against ANP. When UNX was performed in the control groups (sham atrial appendectomy and administration of non specific monoclonal antibodies), mean arterial pressure rose immediately (maximal about 12% within 4 minutes) and transiently (return to pre-UNX values within 20 minutes) after UNX. At the same time, central venous pressure, monitored in the right atrium, tended to decrease slightly. In rats pretreated by right atrial appendectomy or by monoclonal antibodies directed against ANP, arterial pressure increased to the same extent as observed in control groups; this increase however was significantly more prolonged. In control groups, urinary cGMP excretion, the biological marker of ANP, increased twofold in parallel with the natriuretic response. These two responses were blunted in right atrial appendectomized rats and in rats receiving antibodies against-ANP. These results suggest that atrial natriuretic peptide plays a major role in the immediate functional adaptation to unilateral nephrectomy by blunting the increase in blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
The renin-angiotensin system and renal function in kidney transplantation.
The use of converting enzyme inhibitors (CEI) has permitted us to assess the role of the renin-angiotensin system in the control of arterial pressure and renal function in various conditions. In renal transplant recipients treated by azathioprine and steroids, the occurrence of CEI-induced deterioration of renal function is highly suggestive of renal artery stenosis, whereas renal vasodilatation associated with unchanged glomerular filtration rate in response to CEI is indicative of a significant role of native kidneys. In hypertensive recipients without renal artery stenosis, the absence of renal hemodynamic changes after CEI may be predictive of subsequent chronic rejection. The information provided by CEI is rather different in cyclosporine treated subjects. In this setting, no acute effect of CEI on renal hemodynamics is detectable. Whether the renal response to CEI is similar in cyclosporine when compared to conventionally treated patients with renal artery stenosis remains to be demonstrated.
Angiotensin-Converting Enzyme Inhibitors↗
A double blind comparison of perindopril and atenolol in essential hypertension.
A multicentre randomised double-blind trial was performed in order to compare the therapeutic efficacy and acceptability of the angiotensin converting enzyme (ACE) inhibitor perindopril with those of atenolol in mild to moderate hypertension. After one month of placebo, 173 patients with supine diastolic blood pressure (DBP) between 95 and 125 mmHg were randomised to receive perindopril 4 mg once daily or atenolol 50 mg once daily. Monthly assessments were made for three months. Treatment was adjusted at these visits if supine DBP was greater than 90 mmHg; the dose was first doubled (8 mg perindopril or 100 mg atenolol once daily) and then hydrochlorothiazide was added. The pretreatment blood pressure levels were similar in both groups. Supine DBP was 105.5 +/- 0.9 mmHg (n = 85) in the perindopril group and 106.9 +/- 0.9 mmHg (n = 88) in the atenolol group. At the end of the third month, the study target blood pressure (supine DBP less than or equal to 90 mmHg) was achieved in a significantly (P = 0.006) larger percentage of patients in the perindopril group (78%) than in the atenolol group (58%). This appeared to be due to a greater potentiation of the antihypertensive effect by the addition of diuretic to perindopril than to atenolol. The fall in systolic blood pressure was significantly greater in the perindopril group than in the atenolol group (supine: 26.5 +/- 2.0 mmHg vs. 20.6 +/- 2.0 mmHg; P = 0.042) although the fall in DBP was comparable (supine: perindopril 17.4 +/- 0.9 mmHg, atenolol 15.6 +/- 1.1 mmHg; P = 0.195).(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
[Arterial hypertension and chronic kidney failure: recent data].
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Humans↗
Sodium intake influences the effects of atriopeptin on blood pressure and transcapillary fluid shift in the rat.
The influence of chronic changes in sodium intake on the acute effects of atrial natriuretic peptide (ANP) on arterial pressure and fluid translocation was assessed in acutely binephrectomized rats. After 3 weeks of either low sodium or high sodium diet, animals were administered ANP at doses of 0.1 and 1 microgram/kg/min. A marked and irreversible hypotensive response to ANP was observed with the higher infusion rate in the low sodium group, whereas blood pressure did not change significantly in the other groups. The effect of ANP on plasma protein concentration was less marked than that on hematocrit in all groups and was not significantly affected by sodium intake. The effect of both doses of ANP on hematocrit was enhanced in the high sodium group, indicating that the fluid shift out of the intravascular compartment was magnified by high sodium intake.
Animals↗
Successful treatment of Legionella-associated haemolytic uraemic syndrome with acute renal failure and malignant hypertension by prostacyclin (epoprostenol).
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Adult↗
Does age influence the blood pressure and sodium excretion responses to sodium depletion in rats?
Experiments were performed in 3- and 24-month-old male Wistar rats in order to assess the influence of age on the response by systolic blood pressure and sodium excretion to abrupt sodium restriction. In response to the sodium deprivation, urinary sodium excretion was markedly reduced in all animals; however, the cumulative sodium excretion (from days 1 to 6 of depletion) was significantly higher in aged rats (1299 +/- 243 mumol) than in young rats (757 +/- 70 mumol). After 6 days of a low-sodium diet, the systolic blood pressure was similar in both groups. Plasma renin activity was higher in young compared with aged rats (27 +/- 5 versus 14 +/- 3 ng/ml per h). These results indicate that ageing is associated with a significant disturbance in the renal but not the systemic response to an abrupt restriction in sodium intake.
Aging↗