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Biomedical subjects

D Hirsch

Publications and source records attributed to D Hirsch.

At least 73 records · Page 4Linked to original sources
PubMed1986

Intercellular junctions of hyperplastic retinal pigment epithelium.

In rats with retinopathies induced by excess fluorescent light or injections of urethane, the retinal pigment epithelium (RPE) undergoes focal hyperplasia. Neither intravascularly injected horseradish peroxidase or lanthanum nitrate penetrated the sensory retina at these hyperplastic sites. Electron microscopy revealed that this was due to the persistence of intact tight junctions among a single layer of hyperplastic cells facing the sensory retina. These junctions prevented intraocularly injected microperoxidase from passing as well. Cells within the hyperplastic foci were connected only by adherent junctions that presented no permeability barrier.

Animals↗
PubMed1985

Evidence that aldosterone influences transport in target tissues by dissimilar mechanisms.

The present study was performed to answer the question: Is the action of aldosterone on electrolyte transport and electrical properties similar in all target tissues? Studies were performed in vivo in control animals and rats with secondary hyperaldosteronism, caused by a sodium-free diet, to compare the effects of hyperaldosteronism on distal colon with hormone-induced changes in proximal colon. In distal colon aldosterone increased net sodium absorption and potassium secretion approximately threefold. Transmural potential difference increased from -15 +/- 2 to -83 +/- 3 mV (lumen negative) and ISC rose from 167 +/- 26 to 1,023 +/- 17 microA X cm-2. These aldosterone-induced responses were completely inhibited by 0.1 mM amiloride. In contrast, in proximal colon potential difference was unchanged or increased slightly in experimental animals and ISC increased only 28% above control, although increases in net sodium and potassium transport were similar to changes observed in distal colon. Amiloride did not reduce sodium absorption in proximal colon of animals with hyperaldosteronism; ISC was decreased by 43%. These studies demonstrate that rat proximal colon is an aldosterone-sensitive tissue, but that the mechanism by which aldosterone influences sodium transport is not identical in distal and proximal portions of colon.

Aldosterone↗
PubMed1984

Change in inhibitory potential in urine of hyperuricosuric calcium oxalate stone formers effected by allopurinol and orthophosphates.

Allopurinol and orthophosphates were used in the treatment of 25 hyperuricosuric calcium oxalate stone formers. Their urines were tested by the Discriminating Index method, which measures the potential of a urine to retard calcium oxalate precipitation in vitro. The tests were performed before any treatment was begun and about 10 days after the commencement of drug intake. An insignificant effect by allopurinol and a markedly significant effect of orthophosphates on Discriminating Index were found. In a few of the patients, allopurinol seemed to cause a decrease in the urine's potential to retard calcium oxalate precipitation. Therefore the effect of allopurinol in 11 hyperuricosuric patients with no history of calcium oxalate stone formation was tested. In 5 of the 11 patients, the urine's potential to retard calcium oxalate precipitation decreased to levels similar to those of calcium oxalate stone formers. The results of this study suggest that hyperuricosuric calcium oxalate stone formers suffer from the same yet-undefined etiology of stone formation as other calcium oxalate stone formers. The results also question the role of uric acid in calcium oxalate stone formation and the efficacy of allopurinol in preventing this disease. It is suggested that allopurinol may even be related to stone formation in some patients.

Allopurinol↗
PubMed1984

Role of aldosterone in the mechanism of potassium adaptation in the initial collecting tubule.

Studies were performed on the initial collecting tubule of the rat to determine whether potassium adaptation in this nephron segment is aldosterone-dependent. Previous studies demonstrated that chronic potassium loading, in animals with intact adrenal glands, caused an increase in transepithelial potential difference in late distal convolution, an increase in surface density of the basolateral cell membrane, SVBLM, of principal cells in the initial collecting duct, and a rise in plasma aldosterone levels. The present study shows that epithelial changes that characterize dietary potassium loading are not dependent on hyperaldosteronism, since potential difference (-47 +/- 1 vs. 40 +/- 3 mV, lumen negative) and SVBLM (2.91 +/- 0.11 vs. 2.53 +/- 0.09 micron2/micron3) increased significantly (P less than 0.05) in the late distal convolution of adrenalectomized, hormone-replaced animals in which plasma aldosterone levels were maintained at basal values of approximately 5 ng/dl. In addition, these experiments suggest that the initial collecting tubule is sensitive to the action of aldosterone, at physiological plasma levels, since chronic hyperaldosteronism, in the absence of potassium loading, increased SVBLM in initial collecting tubule cells. In contrast to other mineralocorticoid-sensitive tissues, however, neither the acute or chronic administration of aldosterone caused an increase in potential difference in late distal convolution. These results suggest that the mechanism by which aldosterone stimulates electrolyte movement is not identical in all target tissues.

Adrenal Glands↗
PubMed1977

[Correlations between blood pressure, blood volume and plasma renin during therapy with diuretics in essential hypertension. Comparison between the mineralocorticoid antagonist spironolactone and the "loop" diuretic mefruside].

35 patients with benign essential hypertension were treated for 6 weeks with high doses of the mineralocorticoid-antagonist spironolactone (400 mg/day), or with the "loop-diuretic" mefruside (mean maximal dose 110 mg/day). Spironolactone caused greater reductions in blood pressure and blood volume and a more marked increase in plasma renin activity (PRA) than mefruside (p less than 0.05). It appears possible that he weaker antihypertensive effect of mefruside may relate partly to its lesser influence on circulatory volume. With both diuretics, mean decreases in blood pressure were greater in patients with low pre-therapeutic PRA than in patients with normal or high PRA. However, the diuretic-induced changes in blood pressure did not correlate with the associated variations in blood volume or PRA. Thus, the increased blood pressure sensitivity to diuretics in patients with low-renin essential hypertension did not appear to be volume or renin-dependent. Under normal conditions, the maintenance of a constant blood pressure during volume depletion may partly depend on compensatory activation of the sympathetic nervous system. Moreover, patients with low-renin essential hypertension have been found to have decreased adrenergic activity. It seems possible, therefore, that the marked blood pressure sensitivity to diuretic treatment in such patients may be the result of an impaired compensatory sympathetic response to sodium and volume depletion. Analysis of the literature suggests that the diuretic furosemide, a structural relative of mefruside, may also have less blood pressure lowering efficacy in patients with essential hypertension than the distally-acting thiazides, chlorthalidone or spironolactone. Consideration of possible differences in the blood pressure reducing potential of certain diuretics thus appears to be necessary in planning the pharmacotherapy of essential hypertension.

Blood Pressure↗
PubMed1977

Interrelations among blood pressure, blood volume, plasma renin activity and urinary catecholamines in benign essential hypertension.

Interrelations among blood pressure, circulatory volume, plasma renin activity (PRA) and urinary catecholamine excretion rates were studied in normal subjects and in patients with benign essential hypertension. Mean plasma or blood volumes related to lean body mass, products of blood volume and the logarithm of PRA, and catecholamine excretion rates did not differ significantly between normal and hypertensive subjects. In both normal subjects and hypertensive patients, blood pressure levels correlated positively with the noradrenaline excretion rate (r = 0.40 and 0.36, respectively; p less than 0.025) but not with adrenaline excretion, circulatory volume or the volume-renin product. The logarithm of PRA correlated inversely with mean blood pressure in normal subjects (r = 0.40; p less than 0.001) but not in hypertensive patients; however, there was no convincing evidence for an inappropriate blood pressure-PRA relationship as a prominent feature in the hypertensive patients. PRA did not correlate with blood volume. Patients with low PRA relative to sodium excretion (21 per cent of hypertensive population) were consistently normovolemic, but they tended to be older and excreted less (p less than 0.025) adrenaline than patients with normal or high PRA. The patient subgroup with high PRA relative to sodium excretion (11 per cent of population) was hypovolemic (p less than 0.02); despite this, urinary sodium output was high (172 +/- 64 meq/24 hours). These data reveal no evidence for major roles of PRA, circulatory volume and free peripheral catecholamines in the maintenance of benign essential hypertension. Essential hypertension with low PRA is usually not a hypervolemic state, but it may reflect diminished adrenergic activity, factors associated with aging and effects of a high systemic pressure. High PRA in benign essential hypertension may be at least partly a consequence of hypovolemia resulting from high blood pressure-induced sodium diuresis.

Adult↗
PubMed1977

Curable hypertension with unilateral hydronephrosis. Studies on the role of circulating renin.

Among eight patients with unilateral hydronephrosis and hypertension, peripheral plasma renin activity was normal in seven and borderline high in one. Four patients had hydronephrotic/contralateral kidney renin ratios of greater than 1.5, suggesting excessive renin release from the diseased kidney, and ratios between contralateral kidney and peripheral blood of less than 1.2, indicating suppressed renin production in the contralateral kidney. Nephrectomy normalized blood pressure in each of these patients. Two patients had hydronephrotic/contralateral kidney renin ratios of less than or equal to 1.3 or contralateral kidney/periphery ratios of greater than 1.2, suggesting ischemia of the contralateral kidney; pyeloplasty or nephrectomy, or both, failed to improve the hypertension. Postoperative changes in blood pressure correlated with changes in peripheral renin (r = 0.90; P less than 0.01). These data suggest that hypertension associated with unilateral hydronephrosis is partly renin-dependent; and renal vein renin values are helpful in selecting patients for surgery.

Adolescent↗
PubMed1976

[Correlations between blood pressure, blood volume, plasma renin and urinary catecholamines in normal subjects and in patients with benign essential hypertension].

Interrelations between blood pressure, circulatory volume, plasma renin activity (PRA) and urinary catecholamine excretion rates were studied in normal subjects and patients with benign essential hypertension. Mean plasma or blood volumes related to lean body mass, products of blood volume and the logarithm of PRA, and catecholamine excretion rates did not differ significantly as between normal and hypertensive subjects. In both normal subjects and hypertensive patients, blood pressure correlated positively with noradrenaline excretion rate (r = 0.40 and 0.36 respectively; p less than 0.025), but not with adrenaline excretion, circulatory volume or the volume-renin product. The logarithm of PRA correlated inversely with mean blood pressure in normal subjects (r = -0.40; p less than 0.001), but not in hypertensive patients; however, there was no convincing evidence of an inappropriate blood pressure-PRA relationship as a prominent feature in the hypertensive patients. PRA did not correlate with blood volume. Patients with low PRA relative to sodium excretion (21% of hypertensive population) were consistently normovolemic, but tended to be older and excreted less (p less than 0.025) adrenaline than normal or high-PRA patients. The patient subgroup with high PRA relative to sodium excretion (11% of population) was hypovolemic (p less than 0.02); despite this, urinary sodium output was high (172 +/- 64 meq/24 hr). These data reveal no evidence for major roles of PRA, circulatory volume and free peripheral catecholamines in the maintenance of benign essential hypertension. Low-PRA essential hypertension is usually not a hypervolemic state, but may reflect diminished adrenergic activity, factors associated with aging and effects of a high systemic pressure. High PRA in benign essential hypertension may be at least partly a consequence of hypovolemia resulting from high blood pressure-induced sodium diuresis.

Blood Pressure↗
PubMed1976

[Interrelations between blood pressure, blood volume, plasma renin and urinary catecholamines during beta-blockade in essential hypertension (author's transl)].

Studies in 55 patients with benign essential hypertension showed that the beta-blockers bufuralol (22 patients) and propranolol (33 patients) at a dose ratio of 1:4, possess comparable antihypertensive efficacy despite different properties regarding intrinsic sympathomimetic activity. Beta-blocker-monotherapy normalized blood pressure ( less than 140/90 mm Hg) in one fourth of the patients. Body weight and plasma and blood volumes remained unchanged during beta-blockade of four to six weeks duration, the mean plasma potassium was slightly increased. The inhibition of plasma renin activity (PRA) was more pronounced with propranolol (-69%) than with bufuralol (-47%). Wirth both beta-blockers decreases in blood pressure correlated inversely with pre-treatment PRA (p less than 0.05). Propranolol-induced changes in blood pressure correlated also with associated changes in PRA (p less than 0.005); in contrast, no such relationship was observed with bufuralol. The blood pressure effects of bufuralol, however, correlated significantly with changes in urinary noradrenaline excretion (r=0.41; p less than 0.05). Patient sub-groups with low, normal or high pre-treatment PRA in the average showed a comparable pattern of pre-treatment noradrenaline excretion and patients with normal renin levels exreted more adrenaline than those with low renin levels (p less than 0.001). These data are consistent with the concept that in untreated essential hypertension PRA may be an index of adrenergic activiity, the latter representing an important determinant of blood pressure response to beta-blockade. The blood pressure lowering effects of bufuralol in benign essential hypertension seem to be independent of renin and may be related, at least partly, to diminished free peripheral noradrenaline levels.

Adrenergic beta-Antagonists↗
PubMed1975

Control of aldosterone responsiveness in terminal renal failure.

Control of aldosterone responsiveness in terminal renal failure. Plasma aldosterone concentration in 30 hemodialysis patients correlated closely with renin concentration, renin activity or renin and potassium concentrations combined (r is greater than or equal to 0.62; P is less than 0.01), and increased consistently in response to upright posture or corticotropin administration. Aldosterone response to hemodialysis was variable. Significant correlations (r is greater than or equal to 0.65; P is less than 0.01) were demonstrated between postural plasma aldosterone and renin responses, between aldosterone responses to corticotropin and basal plasma aldosterone or renin and potassium values, between hemodialysis-induced changes in plasma aldosterone and those in potassium or renin; but not between various indexes of heparin treatment and aldosterone activity. Bilateral nephrectomy reduced basal plasma renin and aldosterone concentrations and aldosterone responsiveness in five preoperatively normoreninemic or hyperreninemic patients, but not in a hyporeninemic patient. These results demonstrate the complementary roles of circulating renin and potassium in the control of aldosterone release under basal and stimulatory conditions in patients with terminal renal failure. Administration of heparin in dosages used during long-term hemodialysis does not appear to significantly interfere with aldosterone control.

Adrenocorticotropic Hormone↗