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Biomedical subjects

N Stern

Publications and source records attributed to N Stern.

At least 109 records · Page 6Linked to original sources
PubMed1987

Cyclosporin A-induced hyperreninemic hypoaldosteronism. A model of adrenal resistance to angiotensin II.

We studied the effects of cyclosporin A on the renin-aldosterone axis in Sprague-Dawley rats. Two weeks of intragastric administration of cyclosporin A (5 mg/kg/day or or 20 mg/kg/day) resulted in large increases in plasma renin concentration (23 +/- 5, 70 +/- 12, and 79 +/- 11 ng/ml/hr in control rats and rats receiving 5 mg and 20 mg of cyclosporin A, respectively), with no parallel increments in plasma aldosterone. In vitro angiotensin II (ANG II)-stimulated aldosterone secretion by zona glomerulosa cells obtained from cyclosporin A-treated rats was also reduced (4.8 +/- 0.5, 1.5 +/- 0.2, and 0.2 +/- 0.2 ng/10(5) cells in control rats and rats receiving 5 mg and 20 mg of cyclosporin A, respectively). In contrast, in vitro aldosterone response to graded increments of potassium (3.7-10.7 mmol/L) or adrenocorticotropic hormone (ACTH) (10(-11)-10(-8) M) was preserved in cyclosporin A-treated rats. When added in vitro to zona glomerulosa cells from untreated rats, cyclosporin A also attenuated ANG II-stimulated aldosterone secretion, but did not affect potassium or ACTH-mediated aldosterone production. Thus, cyclosporin A-induced hyperreninemic hypoaldosteronism in the rat depends on opposing renal and adrenal effects, with a direct or feedback stimulation of renin secretion and a specific blockade of ANG II-mediated aldosterone production.

Adrenal Glands↗
PubMed1987

Specific action of the lipoxygenase pathway in mediating angiotensin II-induced aldosterone synthesis in isolated adrenal glomerulosa cells.

Angiotensin II (AII) in adrenal glomerulosa cells activates phospholipase C resulting in the formation of inositol phosphates and diacylglycerol rich in arachidonic acid (AA). Although glomerulosa cells can metabolize AA via cyclooxygenase (CO), this pathway plays little role in aldosterone synthesis. Recent evidence suggests that the lipoxygenase (LO) pathway may be important for hormonal secretion in endocrine tissues such as the islet of Langerhans. However, the capacity of the glomerulosa cell to synthesize LO products and their role in aldosterone secretion is not known. To study this, the effect of nonselective and selective LO inhibitors on AII, ACTH, and potassium-induced aldosterone secretion and LO product formation was evaluated in isolated rat glomerulosa cells. BW755c, a nonselective LO inhibitor dose dependently reduced the AII-stimulated level of aldosterone without altering AII binding (91 +/- 6 to 36 +/- 4 ng/10(6) cells/h 10(-4) M, P less than 0.001). The same effect was observed with another nonselective LO blocker, phenidone, and a more selective 12-LO inhibitor, Baicalein. In contrast U-60257, a selective 5-LO inhibitor did not change the AII-stimulated levels of aldosterone (208 +/- 11% control, AII 10(-9) M vs. 222 +/- 38%, AII + U-60257). The LO blockers action was specific for AII since neither BW755c nor phenidone altered ACTH or K+-induced aldosterone secretion. AII stimulated the formation of the 12-LO product 12-hydroxyeicosatetraenoic acid (12-HETE) as measured by ultraviolet detection and HPLC in AA loaded cells and by a specific RIA in unlabeled cells (501 +/- 50 to 990 +/- 10 pg/10(5) cells, P less than 0.02). BW755c prevented the AII-mediated rise in 12-HETE formation. In contrast, neither ACTH nor K+ increased 12-HETE levels. The addition of 12-HETE or its unstable precursor 12-HPETE (10(-9) or 10(-8) M) completely restored AII action during LO blockade. AII also produced an increase in 15-HETE formation, but the 15-LO products had no effect on aldosterone secretion. These studies suggest that the 12-LO pathway plays a key role as a new specific mediator of AII-induced aldosterone secretion.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗
PubMed1986

The catabolism of lung surfactant by alveolar macrophages.

Surfactant was isolated from lung tissue of normal and chlorocyclizine-fed rats. Chlorocyclizine surfactant contained 2.5-3.4 times more phospholipids per mg protein than normal surfactant. Alveolar macrophages, incubated in vitro with normal and chlorocyclizine surfactants hydrolyzed the surfactant phospholipids and incorporated the fatty acids into cellular triacylglycerol. Employing [3H]palmitate-labeled surfactant, it was shown that cells incubated with chlorocyclizine surfactant incorporated 46.2-73.0 nmol of fatty acids per mg protein and were transformed into foam cells. Employing fluorescein or 125I-labeled surfactant, the uptake of surfactant protein by macrophages was shown. No significant differences between protein uptake from normal and chlorocyclizine surfactants were observed. These results suggest that the surfactant phospholipids and protein were catabolized independently.

Animals↗
PubMed1986

Evidence for dopaminergic binding sites in the human adrenal cortex.

Dopamine may be a modulator of aldosterone secretion in man. Whether this effect is extraadrenal or is exerted directly at the adrenal gland via local dopaminergic receptors remains uncertain. This study examined the possibility that dopaminergic binding sites exist in the human adrenal cortex using [3H]spiperone, a butyrophenone with high affinity for dopaminergic receptors of the D2 subtype. [3H]Spiperone binding to membranes prepared from the outer adrenal cortex obtained from eight patients undergoing adrenalectomy was studied. Specific [3H]spiperone binding, defined as binding displacable by 250-fold excess of unlabeled spiperone reached equilibrium within 30 minutes at 4 degrees C and was readily reversible. Binding was consistent with both high affinity (Kd1 = 0.2 to 0.8 nmol/L) and low affinity (Kd2 = 20 to 127 nmol/L) binding states. Binding capacity was 27 to 276 fmol/mg for the high affinity and 63 to 597 fmol/mg for the low affinity binding state. The relative potency in inhibition of [3H]spiperone binding was as follows: antagonists, spiperone greater than domperidone greater than metoclopramide greater than ketanserin greater than (-) sulpiride greater than (+) sulpiride; agonists, dopamine, bromocriptine greater than NPA much much greater than epinephrine. Serotonin and norepinephrine did not affect [3H]spiperone binding. These data suggest the existence of dopaminergic binding sites possibly of the D2 subtype in the human adrenal cortex. The precise location of these sites remains to be determined.

Adrenal Cortex↗
PubMed1986

Circadian rhythm of plasma renin activity in older normal and essential hypertensive men: relation with inactive renin, aldosterone, cortisol and REM sleep.

The 24-h pattern of plasma renin activity (PRA), inactive renin (IR), plasma aldosterone (PA) and cortisol was studied in 13 normal men and 12 male patients with essential hypertension, all of whom were older than 55 years. Following gradual habituation over 4 days to the sleep laboratory and intravenous lines, blood samples were obtained every 2 h between 0900-2100 h and every 30 min between 2100-0900 h, during which sleep was also monitored. Plasma renin activity showed a circadian rhythm in both groups, but mean levels were lower in the hypertensive subjects (0.92 +/- 0.03 versus 1.41 +/- 0.06 ng/ml per h). The circadian rhythm of PRA in older men appeared to follow the same pattern described in younger individuals. Rapid eye movement (REM) sleep was associated with a small decrease in PRA, but this link was only evident in the normotensive group. Mean 24-h IR levels were also lower in the hypertensive group (7.26 +/- 0.18 versus 15.10 +/- 0.47 ng/ml per h) but were not affected by clock-time and generally showed no association with the 24-h PRA cycle. Mean 24-h PA was closely related to cortisol but not to PRA in both groups. Mean PA levels of the two groups were similar. Thus, the PA:PRA ratio was higher in the hypertensive group. The higher basal PA:PRA ratio in older hypertensives that emerged over the 24-h study period may reflect increased sensitivity of the adrenal gland to angiotensin II (ANG II) in hypertension of the elderly.

Aging↗
PubMed1986

Dopaminergic binding and inhibitory effect in the bovine adrenal zona glomerulosa.

Dopaminergic mechanisms may be involved in the regulation of aldosterone secretion in humans and in the rat. Whether these effects are indirect or are exerted directly at the adrenal level has not yet been resolved. We now report the identification of dopaminergic binding sites in the bovine adrenal zone glomerulosa using [3H]spiperone, a butyrophenone with high affinity for D2 dopamine receptors. Specific [3H]spiperone binding (defined as binding displaceable by 10 microns (+)-butaclamol) reached equilibrium within 20 minutes at 22 degrees C, was reversible, and was heat labile (60 degrees C). Binding was of high affinity and saturable with a Kd of 1.8 +/- 0.2 nM and maximal specific binding of 38 +/- 8 fmol/mg (means +/- SEM; n = 18). [3H]Spiperone binding was unaffected by coincubation with angiotensin II, adrenocorticotropic hormone, or KCl. Binding characteristics, including a dissociation constant at the nanomolar range, greater potency of the D2-agonist LY 171555 relative to the D1-agonist SKF 38393 in inhibiting [3H]spiperone binding, and lack of stimulation of cyclic adenosine 3',5'-monophosphate by dopamine (10(-4) M), were consistent with a predominantly D2-receptor. In vitro studies with collagenase-dispersed adrenal zona glomerulosa cells showed that dopamine (10(-4) M) attenuated angiotensin II-stimulated aldosterone secretion. These observations are consistent with a direct inhibitory effect of dopamine on aldosterone secretion in the adrenal zona glomerulosa.

Adrenal Cortex↗
PubMed1986

Altered red cell sodium transport in hypoparathyroidism: relation to serum calcium.

We studied Na transport in red blood cells (RBC) from six patients with hypoparathyroidism (HYPO; 3 postsurgical and 3 idiopathic) and 13 normal subjects. In HYPO, the effect of treatment-induced increases in serum Ca2+ on RBC Na transport also was examined. Na efflux mediated by the ouabain-sensitive Na,K pump and furosemide-sensitive Na,K cotransport (CoT) was examined by flux methodology in RBCs Na loaded to 5 levels of intracellular Na (Nai; 5-90 mM/liter cells) by the p-chloromercuribenzene method. The pump-mediated Na efflux was similar in untreated HYPO patients and normal subjects. Correction of hypocalcemia by vitamin D and oral calcium produced a mean increase in serum Ca2+ from 6.62 +/- 0.23 (+/- SEM) to 8.73 +/- 0.32 mg/dl. In HYPO patients treated with vitamin D and oral calcium, an increasing serum Ca2+ level was associated with significant (P less than 0.01) reductions in pump activity. Further, there was an inverse correlation (r = 0.813; P less than 0.001) between serum Ca2+ and pump-mediated Na efflux rate. RBC Na efflux through the CoT pathway was markedly reduced (P less than 0.05-0.01) in HYPO patients compared to normal subjects at all levels of Nai. Treatment-induced increases in serum Ca2+ had no effect on the reduced RBC CoT function in HYPO. Thus, changes in ambient serum Ca2+ can modulate the activity of the RBC Na,K pump in HYPO, with increases in Ca2+ inhibiting pump function. The markedly decreased RBC CoT activity was not related to associated hypertension or altered renal function and may represent a primary phenomenon in HYPO. These alterations in RBC Na transport may account for the higher Na, in RBCs of HYPO patients.

Adult↗
PubMed1986

Homeostatic fragility in the elderly.

Age-related alterations in adaptation capacity to physiologic changes in physical workload, posture, and water and electrolyte metabolism are reviewed in this article. Other than the increased prevalence of disease in the elderly, normal aging is associated with changes in hormonal secretion patterns, tissue sensitivity to hormones, control of breathing, sleep, and renal function that make this population particularly vulnerable. Orthostatic hypotension, sleep apnea, hypernatremia, hyponatremia, and hyperkalemia, as well as other conditions, are discussed in light of these changes.

Adult↗
PubMed1986

Visual acuity screening of infants and young children with the acuity card procedure.

A new acuity test for infants and young children between 1 and 36 months of age is described. The test was used to evaluate the acuities of 66 infants and young children during a one-day vision screening. At least one estimate of visual acuity was obtained from 63 of the 66 children. Fifty-two of the children completed two monocular acuity tests (or two monocular tests plus a binocular test). The average total test time for these 52 children was less than 15 minutes. Results indicate that the acuity card procedure can be used as a complement to standard optometric tests for large-scale screening of infants and young children.

Child, Preschool↗
PubMed1986

Refractive error and preferential looking visual acuity in human infants: a pilot study.

A clinical pilot study comparing refractive error and preferential looking (PL) visual acuity in infants 2 to 12 months of age is described. The PL visual acuity of 30 normal infants without significant visual disorders was assessed using the Acuity Card Procedure. Near retinoscopy was used to determine refractive error. Infants of this sample had monocular PL visual acuities similar to those established by McDonald et al. in a laboratory setting. Statistical analysis of the data for this sample of infants showed that refractive error did not change systematically from 2 to 12 months of age. We have found that results obtained with the Acuity Card Procedure in a clinical setting agree with infant visual acuity as described in the research literature. Refractive error did not correlate with changes in PL visual acuity in infants 2 to 12 months of age.

Humans↗
PubMed1985

Enhanced 24-hour norepinephrine and renin secretion in young patients with essential hypertension: relation with the circadian pattern of arterial blood pressure.

This study examines the possibility that 24-hour differences in blood pressure (BP) regulation between hypertensive and normotensive subjects is related to changes in 24-hour secretory patterns in circulating pressor hormones. Nine young subjects with normal BP and 9 patients with essential hypertension (EH) were studied during 24-hour recumbency. Every 20 minutes samples were taken to determine plasma norepinephrine (NE) levels and plasma renin activity (PRA). BP was measured every 20 minutes by automatic recording. A distinct circadian rhythm was demonstrated for mean BP, NE and PRA in both groups. Nocturnal reductions in mean BP, NE and PRA related best to the sleep-wakefulness cycle in both groups. Circadian changes in mean BP correlated with NE levels in both normal subjects and patients with EH. The most striking difference between the 2 groups was the absolute levels of mean BP, NE and PRA, which were higher in the EH group at most time points in the 24-cycle. Differences in levels of NE and PRA between the 2 groups were most accentuated during sleep. Thus, young persons with EH show evidence of enhanced sympathetic nervous activity throughout the 24-hour cycle, which is most pronounced during sleep. The multiple sampling approach offers a more sensitive indicator of the role of pressor hormones in BP maintenance.

Adult↗