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Biomedical subjects

A Mimran

Publications and source records attributed to A Mimran.

At least 19 recordsLinked to original sources
PubMed1992

[Arterial hypertension, hyperinsulinism and insulin resistance].

The incidence of hypertension is increased in obesity, a state associated with an insulin resistance syndrome. By using an euglycemic clamp method, Ferrannini et al. demonstrated the existence of an insulin resistance state in patients with essential hypertension. However, the body mass index of the subjects studied appeared to be slightly excessive. This abnormality has not been observed in patients with secondary hypertension. Insulin resistance is probably localized to peripheral tissues such as muscles and may be associated with other cellular abnormalities. Can insulin resistance, characterized by a raised circulating insulin concentration in the presence of normal blood glucose, be responsible for certain "modifications" associated with essential hypertension? Insulin induces sodium retention and increases the aldosterone-secreting effect of angiotensin II. These effects are likely to promote a rise in blood pressure and an increase in the sensitivity of vessels to endogenous substances. Moreover, insulin is a known growth factor and is involved in lipoprotein metabolism. If insulin resistance plays an important role in the maintenance of complications of essential hypertension, it is important that the treatments used tend to correct this anomaly. Thiazide diuretics and beta-blockers aggravate insulin resistance while angiotensin converting-enzyme inhibitors correct this condition.

Adult↗
PubMed1992

Renal effects of antihypertensive agents in parenchymal renal disease and renovascular hypertension.

Treatment of hypertension by conventional antihypertensive medications usually has no significant effect on renal function in patients with essential hypertension and normal glomerular filtration rate. In this condition, new agents such as angiotensin-converting enzyme (ACE) inhibitors and calcium-channel blockers (CCBs) also do not appear to modify renal function. Reduction of arterial pressure is crucial for renal protection in patients with chronic renal disease and the effect of the new agents on the progression of renal failure remains unknown despite some promising reports. In patients with renovascular hypertension, mainly those with bilateral stenosis or stenosis of a solitary kidney, the use of ACE inhibitors may be associated with reversible renal deterioration, particularly in subjects with already impaired renal function and receiving diuretics. In this situation, reduction in arterial pressure by CCBs does not appear to lead to renal deterioration.

Antihypertensive Agents↗
PubMed1992

Renal interstitial pressure and tubuloglomerular feedback control in rats during infusion of atrial natriuretic peptide (ANP).

Atrial natriuretic peptide (ANP), injected at physiological concentrations, is known to induce both natriuresis and diuresis. It has been suggested by some investigators that these changes result from an increasing glomerular filtration rate (GFR), but others have been unable to demonstrate an increased GFR. The tubuloglomerular feedback (TGF) mechanism is an important regulator of GFR, and the sensitivity of TGF is decreased during ANP administration. Furthermore, resetting of TGF is, in most instances, related to changes in renal interstitial hydrostatic and oncotic pressures. It is also known that ANP may increase capillary permeability which may change renal interstitial pressure. The present study was performed to examine renal interstitial pressures and the TGF mechanism during ANP infusion. In accordance with previous studies, TGF sensitivity was found to be decreased. The tubular flow rate which elicited half the maximal drop in stop-flow pressure (Psf) was increased from 18.5 to 25.7 nl min-1. In contrast, ANP infusion resulted in a decreased interstitial hydrostatic pressure and an increased interstitial oncotic pressure. From previous experiments, such changes in interstitial pressures would be expected to increase TGF sensitivity. The changes in interstitial pressure cannot, therefore, directly explain the resetting of the feedback mechanism. In conclusion, the present paper shows a decreased renal net interstitial pressure after intravenous administration of ANP.

Animals↗
PubMed1992

Adaptation to sodium restriction in renin-immunized spontaneously hypertensive and normotensive rats.

The influence of active immunization against renin on the systemic and renal adaptation to abrupt suppression of dietary sodium was assessed in spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats. Very low level of plasma renin activity and no response of circulating renin to sodium restriction were observed in immunized rats. The final systolic arterial pressure achieved in immunized SHR (144 +/- 3 mmHg) was similar to that observed in nonimmunized WKY (137 +/- 4 mmHg), and no influence of renin immunization on renal blood flow was observed in both strains maintained on ad libitum sodium intake. Dietary sodium restriction was associated with a consistent decrease in arterial pressure in immunized rats, whereas no change occurred in sham-immunized rats. No impairment in the renal adaptation was detected in immunized rats (6-day cumulative sodium excretion of 1.67 +/- 0.2 and 1.65 +/- 0.3 mmol in immunized SHR and WKY, respectively, and 1.50 +/- 0.2 and 1.21 +/- 0.2 mmol in sham-immunized SHR and WKY rats). These studies indicate that renin immunization decreases arterial pressure but does not affect renal adaptation to dietary sodium restriction in hypertensive and normotensive rats.

Adaptation, Physiological↗
PubMed1992

Sodium and left ventricular mass in untreated hypertensive and normotensive subjects.

To determine whether urinary sodium excretion (a rather rough estimate of sodium intake) can influence left ventricular mass independently of arterial pressure, 91 untreated subjects with essential hypertension and 50 normotensive subjects of similar age were studied. Left ventricular mass index (M-mode echocardiography) was positively correlated with urinary sodium excretion in hypertensive (r = 0.22, P less than 0.01) as well as normotensive subjects (r = 0.22, P less than 0.05), and systolic arterial pressure was correlated only in hypertensive subjects (r = 0.23, P less than 0.01). When hypertensive subjects were divided into groups with appropriate or inappropriate left ventricular mass by reference to a theoretical optimal left ventricular mass for each subject's level of systolic arterial pressure, left ventricular mass was appropriate in 68% and inappropriate in 32% of subjects. Urinary sodium excretion was higher in subjects with inappropriate left ventricular mass compared with those with appropriate left ventricular mass. In conclusion, sodium excretion may be an important modulator of the influence of arterial pressure on the left ventricle in normotensive subjects and subjects with essential hypertension.

Adolescent↗
PubMed1992

Antihypertensive therapy in renal disease and transplantation.

HYPERTENSION AND RENAL DISEASE: In experimental models of renal disease not only protein intake and hyperlipidaemia but also hypertension may contribute to the progressive deterioration in renal function; in these models an imbalance in intrarenal haemodynamics appears to be a particularly important factor. ANTIHYPERTENSIVE THERAPY: A reduction in arterial pressure can alter the course of human chronic renal disease. However, it is not clear whether any one class of antihypertensive drug is superior to any other class in these patients. Angiotensin converting enzyme (ACE) inhibitors may prevent the progression from incipient to overt diabetic nephropathy and afford better protection than conventional treatment. In patients with non-diabetic renal disease there is no unequivocal evidence for a protective effect. In renal transplant recipients, mainly those taking cyclosporine, ACE inhibitors are equally effective compared to calcium antagonists in the control of hypertension, but their renal effects in transplant recipients without renal artery stenosis have not yet been assessed.

Acute Kidney Injury↗
PubMed1992

[Left systolic ventricular function and metabolic disorders in untreated hypertensive patients].

Previous studies have shown that essential hypertension is frequently associated with insulin resistance and hyperinsulinism. Because insulin may exert a direct positive inotropic as well as chronotropic effect and controlled the initiation of peptide chains in the heart, we tested the hypothesis that insulin may be a determinant of myocardial hypertrophy and contractility. The relation between glucose metabolism (assessed by the oral glucose tolerance test) and left ventricular (LV) mass and function (assessed by echocardiography) was explored in 47 never-treated lean essential hypertensive patients (EH) of short duration and 19 normotensive subjects (NT). A greater number of EH versus NT (23 vs 5%) had an abnormal glucose tolerance. The fasting insulin-to-glucose ratio was significantly higher in EH as compared to NT. Fasting as well as integrated serum insulin to glucose values ratio were positively correlated with heart rate (r = 0.35, p < 0.05, r = 0.38, p < 0.05) and the LV end-systolic stress to volume ratio (r = 0.48, p < 0.001, r = 0.54, p < 0.001) but not with LV mass (r = 0.02, r = 0.02) in EH. When EH were divided into those with normal (n = 36) and supernormal (n = 11) LV contractility based on the relationship between LV fractional shortening and LV end-systolic stress, integrated insulin level and fasting insulin to glucose ratio were markedly higher in patients with supernormal LV contractility, whereas arterial pressure, heart rate, urinary sodium excretion, and plasma renin activity were similar in the two groups. We concluded that hyperinsulinemia and LV hypercontractility are associated in patients with hypertension of short duration. If chronic hyperinsulinemia is to be causally related to hypertension, one would have to postulate that the effects (inotropism and chronotropism) of insulin on the heart can be dissociated from the resistance to the glucose-lowering action of insulin.

Blood Glucose↗
PubMed1992

Aging and sodium homeostasis.

Deterioration of glomerular filtration rate appears to be progressive throughout life whereas sodium intake tends to remain constant. The influence of aging may be amplified by intrinsic renal disease, unilateral nephrectomy or renovascular abnormalities. Changes in the tubular reabsorption of sodium will allow the excretory capacity of the kidney to adjust to fluctuations in normal sodium intake. However, restriction of dietary sodium may be associated with a sluggish renal response; a sodium wasting state that could lead to significant deterioration in renal function and orthostatic hypotension, may occur. Conversely, increasing dietary sodium in older subjects may result in a rise in arterial pressure more often than in younger subjects. Dietary sodium restriction should be carefully controlled in elderly subjects.

Aging↗
PubMed1991

[Functional reversibility of chronic cyclosporine nephrotoxicity in patients after kidney transplantation].

The long term use of cyclosporin in renal transplant recipients may be complicated by chronic nephrotoxicity, evidenced by renal functional deterioration and suggestive histological lesions. In 11 renal transplant recipients treated with cyclosporin since 28 +/- 5.8 months, we reduced (n = 6) or stopped (n = 5) this drug after chronic nephrotoxicity was diagnosed. Five months later, we conducted hemodynamic studies and observed significant increases in renal plasma flow (I131 hippuran clearance from 239.5 +/- 106 to 327 +/- 50 ml/min/1.73 m2) and glomerular filtration rate (DTPA-TC clearance from 43 +/- 15 to 67 +/- 10 ml/min/1.73 m2) and a decrease in renal vascular resistances. We suggest that cyclosporin-associated chronic nephrotoxicity is accompanied by some degree of reversible vasoconstriction, or that histological lesions, particularly cyclosporin arteriolopathy, can disappear after cyclosporin withdrawal.

Chronic Disease↗
PubMed1991

Converting enzyme inhibitors and renal function in essential and renovascular hypertension.

Converting enzyme inhibitors (CEI) are useful in the treatment of hypertension. However, acute renal deterioration may occur in some conditions in association with the crucial role of angiotensin in the regulation of glomerular filtration rate (GFR), such as volume depletion, severe stenosis of both renal arteries, and stenosis of a single functioning kidney. CEI-induced acute renal failure can develop in the absence of a fall in systemic pressure, is facilitated by prior sodium depletion, and is reversible upon discontinuation of treatment. In a personal study conducted in 28 patients with CEI-induced renal dysfunction (reversible after discontinuation of CEI), the incidence of stenosis of large renal vessels was 61%, whereas 39% of these subjects had no significant renal artery abnormalities. Although the occurrence of such a complication is not a convincingly accurate predictor of the existence of renovascular hypertension, angiographic detection of renal artery stenosis (bilateral or on a single-functioning kidney) may be justified in some of these patients.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1991

Renal changes associated with cyclosporine in recent type I diabetes mellitus.

The effects of cyclosporine A treatment on arterial pressure and renal function were assessed in 11 young patients with type I diabetes of short duration. Cyclosporine was started at 7.5 mg/kg/day, progressively decreased to 6.3 mg/kg/day at 6 months, and then continued at a lower dose (4.1 mg/kg/day) for an additional 3 months in patients in whom remission of insulin dependency was obtained (n = 6). After 3 months of cyclosporine, a slight but significant increase in arterial pressure (+5.2 +/- 1.5 mm Hg), a rise in renal vascular resistance (approximately 20%), a decrease in glomerular filtration rate (approximately 25%), and a fall in filtration fraction were observed. Such changes were sustained after 6 and eventually 9 months of therapy. The decrease in glomerular filtration rate observed during cyclosporine treatment contrasted with the lack of change in simultaneously estimated creatinine clearance; in fact, the creatinine clearance/glomerular filtration ratio increased from 1.07 +/- 0.05% to 1.33 +/- 0.09% within 3 months of cyclosporine therapy, thus suggesting an enhanced tubular secretion of creatinine. Plasma renin activity and urinary excretion of kallikrein decreased significantly (approximately 50%), whereas plasma aldosterone concentration remained unaltered and plasma concentration of potassium increased during cyclosporine therapy. These changes were observed in the presence of a constant urinary excretion of sodium and potassium and a constant body weight. All parameters returned to pretreatment values within 3 months after cessation of cyclosporine. These results indicate that cyclosporine given for 6-9 months at a moderate dose causes a deleterious but reversible effect on arterial pressure and renal function in young diabetic patients.

Adolescent↗
PubMed1991

Blood pressure reduction as a preventive treatment of diabetic nephropathy.

Arterial hypertension is present in 10-80% of newly diagnosed Type 2 diabetics, and in 30-50% of Type 1 diabetics after some years. In patients with overt nephropathy, correction of hypertension is associated with a reduction in the rate of decline of glomerular filtration rate. In most patients without clinical diabetic nephropathy, arterial pressure remains within normal limits as defined by usual criteria, whether or not microalbuminuria is present. Short-term studies of Type 1 diabetics with microalbuminuria suggest that angiotensin-converting enzyme inhibitors result in a fall in urinary albumin excretion rate more than calcium antagonists and diuretics. Additional studies assessing the long-term effect of different antihypertensive agents on the evolution of early diabetic nephropathy are needed before the superiority of any drug can be claimed. In addition, non pharmacological approaches, including optimal glycemic control as well as modification of dietary sodium and serum lipid profile, may alter the progressive course of elevation in arterial pressure and decline in renal function. The optimal level of blood pressure for diabetic patients remains to be determined.

Albuminuria↗
PubMed1991

[Extravascular transfer of fluids and proteins induced by endothelin in the binephrectomized rat].

To test the possibility that endothelin affects extracellular fluid partition between plasma and interstitium, we compared the effects of endothelin and vehicule in euvolemic binephrectomized anesthetized rats by measuring changes in hematocrit and plasma protein concentration. Forty-five minutes infusion of endothelin (25 ng/kg/min) induced a progressive increase in blood pressure by 1.7 +/- 1.3, 6.8 +/- 1.5 and 12.1 +/- 2.1% at 15, 30 and 45 min respectively from a basal value of 99 +/- 5 mmHg. Hematocrit increased by 8.0 +/- 0.6% (p less than 0.001) after 45 min of infusion, while the vehicle had no significant effect (+ 1.7 +/- 0.7%). The same increase in hematocrit was observed in binephrectomized and splenectomized rats. The calculated loss of plasma volume during endothelin infusion was 13.1 +/- 0.9% as compared to 2.1 +/- 1.2% in rats receiving the vehicle. Plasma protein concentration increased by only 4.2 +/- 0.6% suggesting an extravasation of proteins. To document and localize an alteration in vascular leak of proteins induced by endothelin, albumin-bound Evans Blue (EB) extravasation was measured spectrophotometrically in different tissues after extraction by formamide. Endothelin increased vascular permeation of EB-albumin in skeletal and cardiac muscle, intestine and mesentery. No change was observed in brain, liver, spleen as compared to rats receiving the vehicle. In addition, endothelin infusion elicits a three fold increase of the plasma immunoreactive atrial natriuretic peptide (ir-ANP) concentration (from 196 +/- 50 to 722 +/- 203 pg/ml; p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

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↗