Search PubMed⌕ Search

Biomedical subjects

M Epstein

Publications and source records attributed to M Epstein.

At least 253 records · Page 14Linked to original sources
PubMed1985

Effects of diltiazem and manganese renal hemodynamics: studies in the isolated perfused rat kidney.

The effects of the organic calcium antagonist diltiazem (DIL) upon the alterations in renal hemodynamics produced by norepinephrine (NE) were assessed in the isolated perfused rat kidney. In the presence of propranolol, the administration of NE (3 X 10(-7)M) caused sustained reductions in renal perfusate flow (RPF) and glomerular filtration rate (GFR). The administration of 10(-5) M DIL to NE-treated kidneys did not reverse the NE-induced decrease in RPF. In contrast, DIL produced a striking reversal of the NE-induced decrease in GFR. In the absence of NE-treatment, DIL did not alter GFR or RPF. We conclude that NE-induced constriction of major postglomerular resistance vessels of the rat kidney is not inhibited by DIL. In contrast, the DIL-induced increase in GFR of the NE-treated kidneys indicates that the NE-constriction of preglomerular resistance vessels is inhibited by this organic Ca entry blocker. Under identical conditions, manganese, an inorganic calcium entry blocker, reversed the NE-induced reductions in both RPF and GFR, indicating that although both responses depend upon Ca entry, only the latter is sensitive to DIL. These data are, therefore, consistent with the postulate that different regions of the renal vasculature are heterogeneous with regard to the mechanisms mediating NE-induced vasoconstriction.

Animals↗
PubMed1985

Nitrendipine-induced stimulation of renin release by the isolated perfused rat kidney.

The direct effects of the organic calcium antagonist nitrendipine upon renin release were assessed using the isolated rat kidney perfused at constant pressure. This model circumvents the indirect actions of vasodilating agents by artificially maintaining perfusion pressure constant, thereby avoiding the hypotensive effects associated with the systemic administration of such agents. Renin release as assessed by radioimmunoassay was stimulated 2.6-fold upon the administration of 10(-6) M nitrendipine. Since this stimulation of renin release occurred in the absence of any alteration in perfusion pressure, we conclude that it represents a direct action of nitrendipine. This finding is in support of the current hypothesis concerning the inverse relationship between cytosolic Ca2+ and renin secretory rate, and suggests that Ca entry into the juxtaglomerular cells of the juxtaglomerular apparatus is sensitive to blockade by organic calcium antagonists such as nitrendipine.

Angiotensin I↗
PubMed1985

Beta blockers and renal function: a reappraisal.

The chronic use of propranolol is characterized by 10%-20% decrements of renal plasma flow (RPF) and glomerular filtration rate (GFR). The results of most investigations, however, suggest that the use of nadolol, a long-acting nonselective agent, spares renal function. Similarly, intrinsic sympathomimetic activity (ISA)-positive and cardioselective beta-adrenergic inhibitors and the combined alpha-beta blocker, labetalol, appear to preserve renal hemodynamics. The reason(s) for the apparent disparate effects of various beta blockers is uncertain. The pathophysiological mechanisms are probably multifactorial and relate to either diminished cardiac output or increased renal vascular resistance, or both. It is possible that inhibition of renal vasodilator mechanisms plays a role. The explanation for the relative absence of adverse effects with a given medication probably varies from agent to agent. The clinical implications of beta-blocker-induced renal changes are presently unknown. The alterations are probably not clinically important in patients with normal renal function. In patients with underlying renal insufficiency, there is no reason to avoid the use of beta-adrenoceptor blockers. In some patients, however, one may wish to prescribe those beta blockers that tend to spare RPF and GFR.

Adrenergic beta-Antagonists↗
PubMed1985

Effects of water immersion on plasma catecholamines in decompensated cirrhosis. Implications for deranged sodium and water homeostasis.

Although an impairment in renal sodium and water excretion is a commonly encountered clinical problem in cirrhotic patients, the mechanisms responsible for this abnormality are uncertain. Norepinephrine (NE) levels are elevated in some patients with decompensated cirrhosis, but a causal relationship between these levels and impaired sodium and water excretion has not been established. Since in normal man, water immersion to the neck (NI) results in a preferential central hypervolemia, and since theoretical considerations suggest that central hypervolemia might suppress NE, we designed the present study to determine if the natriuretic and diuretic responses of cirrhotic patients to NI are mediated by a decrease in NE. 16 cirrhotic patients with ascites were studied on two occasions: during a seated control study and during 4 h of NI: NE, determined by radioenzymatic assay, was measured hourly. 15 of the 16 patients manifested a marked diuresis, and 12 had a natriuresis that equalled or exceeded that documented in normal subjects during NI. NI did not alter mean NE, with 9 subjects manifesting an increase of NE as compared with the prestudy hour. Furthermore, peak urinary sodium excretion and flow rate varied independently of prestudy NE (r = 0.163 and -0.173, respectively), change in NE (r = 0.256 and 0.239), as well as nadir NE levels (r = 0.118 and -0.039). The demonstration of a natriuresis and a diuresis in a majority of the subjects, occurring without concomitant suppression of plasma NE, suggests that NE does not constitute the prepotent determinant in the impaired sodium and water excretion of many patients with advanced liver disease.

Adult↗
PubMed1985

Aging and the kidney: clinical implications.

Beyond the age of 30, kidney size begins to decrease, and there are accompanying decreases in total renal blood flow, outer cortical flow, glomerular filtration rate and the ability both to conserve and to excrete sodium. There is also a decline in concentrating ability and possibly in diluting ability. These changes make the elderly patient more susceptible both to hyponatremic and to hypernatremic states.

Acute Kidney Injury↗
PubMed1985

Reversal by the calcium antagonist nisoldipine of norepinephrine-induced reduction of GFR: evidence for preferential antagonism of preglomerular vasoconstriction.

We have demonstrated previously that the organic Ca++ antagonist diltiazem augments the glomerular filtration rate (GFR) of the isolated perfused rat kidney during norepinephrine (NE) - induced vasoconstriction. These earlier studies, however, did not elucidate the precise mechanism or site of action responsible for this effect. Nisoldipine (NIS) interacts with the same Ca+2 channels as diltiazem but differs in its physicochemical properties, binding characteristics and tissue specificity. We examined, therefore, the effects of NIS using an identical model. Renal perfusate flow and GRF were assessed in the isolated perfused rat kidney under conditions of constant renal perfusion pressure (100 mm Hg). NIS (10(-7) M) completely reversed the NE-induced reduction in GFR but was significantly less effective in augmenting renal perfusate flow. In additional series of experiments, filtration pressure was estimated during these manipulations by monitoring ureteral pressure during ureteral occlusion (stop-flow pressure). The NE-induced decrease in GFR was accompanied by a reduction in stop-flow pressure, which was abolished by the subsequent administration of NIS. Thus, nisoldipine preferentially attenuated NE-induced constriction of preglomerular resistance vessels but was less effective in reversing the effects of NE on postglomerular arterioles. These findings indicate that separate postreceptor mechanisms mediate the activation of pre- and postglomerular vessels by NE.

Animals↗
PubMed1985

Relationship between urine flow rate and prostaglandin E excretion in human beings.

Although an increase in urine flow rate has been shown to augment urinary prostaglandin E (PGE) excretion, the relationship between these two variables has not been quantitated. Because we have previously shown that water immersion to the neck induces diuresis and augmentation of PGE excretion, we utilized water immersion to the neck to assess kinetically the relationship between changes in flow rate and PGE excretion. Fourteen normal male subjects were studied twice during 4 hours of water immersion to the neck, once after 11 hours of fluid deprivation and again during moderate hydration. PGE excretion as determined by radioreceptor assay was measured each hour. When subjects deprived of fluids underwent immersion to the neck, flow rate increased from 0.5 ml/min (control) to 1.5 ml/min, and PGE excretion rose from 1.4 to 2.6 ng/min (both p less than 0.01). In contrast, when subjects were studied during hydration, flow rate increased from 4.1 to 7.2 ml/min and PGE excretion increased from 8.1 to 13.0 ng/min at the same time intervals (both p less than 0.01). There was a significant positive correlation between flow rate and PGE excretion during both fluid deprivation and hydration. Were there an effect, independent of flow rate, of hydration on PGE, the slope of these two regression lines would differ. When the regression line slopes of these relationships were analyzed by the F test, there was a statistically significant (p less than 0.01) difference between the two regression coefficients. Our data suggest that, in addition to the previously characterized relationship between flow rate and PGE excretion, there is also a direct effect of hydration on PGE excretion.

Adult↗
PubMed1984

Activation mechanisms of human renal artery: effects of KCl, norepinephrine and nitrendipine upon tension development and 45Ca influx.

The activation of human vascular smooth muscle by KCl-induced depolarization or norepinephrine and the inhibition produced by nitrendipine were studied in the isolated human renal artery. The contractile response of arterial rings to 80 mM KCl was abolished when extracellular Ca2+ was removed, and was inhibited by nitrendipine (IC50 = 10(-8) M). In contrast, a residual, transient contractile response to norepinephrine remained when extracellular Ca2+ was removed and the norepinephrine-induced contractions obtained in the presence of extracellular Ca2+ were not blocked by nitrendipine. KCl caused a stimulation of 45Ca influx which was completely prevented by 10(-6) M nitrendipine. Norepinephrine also caused a stimulation of 45Ca influx; however, the norepinephrine-induced 45Ca influx was not prevented by 10(-6) M nitrendipine. These findings are consistent with the concept that depolarization-induced activation of the human renal artery is primarily dependent upon a stimulation of Ca2+ influx; whereas activation by norepinephrine involves the release of intracellular Ca2+ in addition to the activation of a separate, receptor-operated Ca2+ influx pathway.

Biological Transport↗
PubMed1984

Relationship between plasma arginine vasopressin and renal water handling in decompensated cirrhosis.

Although an impairment in renal water excretion is a commonly encountered clinical problem in cirrhotic patients, the mechanisms responsible for this abnormality are uncertain. ADH levels are elevated in some patients with decompensated cirrhosis, but a causal relationship between these levels and impaired water excretion has not been established. Since in normal man, water immersion to the neck (NI) results in a preferential central hypervolemia (CV), without plasma compositional change, and a resultant suppression of AVP, we designed the present study to determine if the diuretic response of cirrhotic patients to NI is mediated by a decrease in AVP. 17 cirrhotic patients with ascites were studied following 14 h of dehydration on two occasions: during a seated control study (C) and during 4 h of NI. AVP, determined by RIA, was measured every 30 min. 12 of the 17 patients manifested a diuresis that equalled or exceeded that documented in normal hydropenic subjects during immersion. NI did not alter mean AVP as compared with either the pre-study hour or those of the corresponding control study. Furthermore, peak V and CH2O varied independently of prestudy AVP (r = -0.116), mean change in AVP (r = -0.060), as well as nadir AVP levels (r = -0.122). The demonstration of a diuresis in some of the subjects, occurring without concomitant suppression of plasma AVP, suggests that ADH may constitute a permissive rather than pivotal factor in the impaired water excretion of many patients with advanced liver disease.

Adult↗
PubMed1984

Water immersion and the kidney: implications for volume regulation.

Studies from this laboratory have demonstrated that head-out immersion in isothermic water causes a cephalad redistribution of blood volume. The resultant central hypervolemia induces a marked natriuresis and diuresis and suppression of plasma renin activity, plasma aldosterone, and plasma arginine vasopressin. All of these changes are thought to be attributable to stimulation of cardiopulmonary receptors. Immersion also produces an augmentation of prostaglandin E (PGE) excretion, which reflects increased renal PGE synthesis. The ability of immersion in induce a prompt and profound central hypervolemia, without concomitant alterations in plasma composition, indicates that immersion might be a preferred investigative tool for assessing the effects of volume expansion on renal function and hormonal responsiveness in both normal individuals and patients with edematous disorders. In addition, this model constitutes an appropriate tool for simulating weightlessness.

Blood Volume↗