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Biomedical subjects

M Epstein

Publications and source records attributed to M Epstein.

At least 235 records · Page 13Linked to original sources
PubMed1987

Modification by dihydropyridine-type calcium antagonists of the renal hemodynamic response to vasoconstrictors.

The effects of dihydropyridines on the renal response to vasoconstrictors was assessed using the isolated perfused rat kidney. During norepinephrine-induced vasoconstriction, dihydropyridines preferentially alter glomerular filtration rate and have less of an effect on perfusate flow. Calcium channel antagonists such as nitrendipine and nisoldipine augment glomerular filtration rate, whereas calcium channel agonists depress glomerular filtration rate. A preferential effect on glomerular filtration rate is also observed with the administration of nitrendipine to kidneys during vasoconstriction induced by angiotensin II. In contrast, nitrendipine does not exert a preferential augmentation of glomerular filtration during vasoconstriction mediated by KCl-induced depolarization. These observations are discussed in the context of the cellular mechanisms of dihydropyridines. It is proposed that differing postreceptor processes couple receptor occupation to smooth muscle contraction in afferent and efferent arterioles, and that a selective inhibition of receptor-mediated afferent vasoconstriction may underlie the renal hemodynamic response to dihydropyridines.

Animals↗
PubMed1987

Fixed-dose combination medications for the treatment of hypertension: a critical review.

Aside from the retrospective analysis of Clark and Troop (1), no large-scale controlled study has been designed specifically to assess the advantages and disadvantages of fixed-dose antihypertensive combinations. The use of fixed-dose antihypertensive combinations is no longer the anathema of the academician. The principal advantages of fixed-ratio combinations are simplicity of use, potentiation of blood-pressure-lowering efficacy, and potential counterbalancing of certain side effects. An additional advantage might be improvement in broad-based cost effectiveness, that is, a potential reduction in the need for frequent laboratory surveillance and in the frequency of office visits. The principal disadvantage is the relative inflexibility of dosage adjustment. Antihypertensive therapy should be initiated with a single drug preparation, with subsequent substitution of a combination product when appropriate. Tables 4 and 5 summarize, respectively, some of the important factors to consider and the theoretical requirements when contemplating the use of fixed-dose antihypertensive combinations. Diuretic/beta-blocker combinations are particularly attractive because of the enormous long-term experience with each component, their proven efficacy and additional salutary effects, their generally acceptable and sometimes offsetting side effects, and their potential for once-a-day dosing. It seems likely that CEI/diuretic and perhaps calcium-channel blocker/diuretic combinations also have great merit.

Adrenergic beta-Antagonists↗
PubMed1986

Renal prostaglandins and the control of renal function in liver disease.

Recent evidence suggests that renal prostaglandins play a major role in the control of renal hemodynamics and function in patients with advanced liver disease. The available data suggest that alterations in renal prostaglandin metabolism participate in the pathogenesis of at least three prominent renal complications of liver disease: sodium retention, impaired renal diluting ability, and the hepatorenal syndrome. Nonsteroidal anti-inflammatory agents that inhibit cyclooxygenase activity favor sodium retention and diminish renal plasma flow and glomerular filtration rate in patients with decompensated cirrhosis. The clinical caveat emerging from these observations is that nonsteroidal anti-inflammatory agents, which inhibit cyclooxygenase activity, should not be prescribed for sodium-retaining patients with decompensated liver disease.

Animals↗
PubMed1986

Further characterisation of the inotropic effect of a bufodienolide glycoside--an endogenous ouabain like compound.

A ouabain like compound obtained from toad skin and plasma and identified to be a steroidal bufodienolide glycoside was found to displace ouabain from its binding site and to inhibit Na+-K+ ATPase, and have positive inotropic effects on cardiac muscle. The ionic and rate dependence of this positive inotropy was studied in the frog atrium. The effect was dependent on extracellular potassium, sodium, and calcium concentrations and on the rate of stimulation, which is similar to the properties of cardiac glycosides. Occasionally, the compound gave transient or even negative inotropic responses, as do the glycosides. The action potential configuration was also affected by the compound in the same complex pattern as is that of cardiac glycosides. It is concluded that the endogenous bufodienolide compound has the same physiological effects as cardiac glycosides. Since the same compound is present in toad plasma it may serve as an intrinsic humoral regulator of cardiac contractility. This study is the first detailed characterisation of the cardioactive properties of this compound.

Action Potentials↗
PubMed1986

Reversal of renal and smooth muscle actions of the thromboxane mimetic U-44069 by diltiazem.

U-44069 is a stable prostaglandin (PG) H2 analogue and a potent vasoconstrictor. Its in vivo and in vitro actions mimic those of thromboxane A2. We have studied the effects of the calcium antagonist diltiazem upon the vasoconstriction induced by U-44069 using isolated rat aortic smooth muscle and isolated perfused rat kidney (IPRK). The administration of 10(-6)M U-44069 elicited maximally effective contractions in isolated aortic rings and increased 45Ca uptake from a control value of 285 +/- 6 mumol/kg to 344 +/- 8 mumol/kg. Diltiazem reduced U-44069-induced tension development and 45Ca uptake of isolated aortic smooth muscle 73 +/- 2 and 91 +/- 3%, respectively. The dose dependency of each of these effects of diltiazem was similar (EC50 = 369 nM and 334 nM for tension and 45Ca flux, respectively). When administered to the IPRK, 10(-6) M U-44069 caused a 82 +/- 3% decrease in glomerular filtration rate (GFR) and a 80 +/- 4% decrease in filtration fraction but reduced renal perfusate flow (RPF) only 13 +/- 8% (P less than 0.005). Diltiazem completely reversed the actions of U-44069 on the IPRK (EC50 = 288 nM and 323 nM for GFR and RPF, respectively). Diltiazem thus inhibited U-44069-induced tension development and 45Ca uptake by vascular smooth muscle and increased GFR within identical dose ranges. The contractile response of isolated rat glomeruli was also assessed. U-44069 reduced the volume of isolated glomeruli, but this action was neither prevented nor reversed by diltiazem. These results are consistent with the hypothesis that diltiazem increased GFR by inhibiting U-44069-induced Ca influx at preglomerular vessels.

Animals↗
PubMed1986

Spectrum of deranged sodium homeostasis in essential hypertension.

Essential hypertension is thought to produce a uniform exaggerated natriuresis and diuresis. Because validation of this formulation in humans is incomplete, the natriuretic and diuretic responses to acute volume expansion were characterized by using water immersion to the neck. This method provides a volume stimulus identical to that induced by 2 L of saline without plasma compositional change. Twenty-seven subjects with essential hypertension were studied on three occasions in the seated posture while in balance on a 10 mEq Na, 100 mEq K diet: during the seated control study, during 4 hours of head-out immersion, and during saline infusion (2 L/2 hours). Four subjects had exaggerated urinary Na excretion in response to neck immersion (Group 3), and 16 had a normal response (Group 2) indistinguishable from that of 15 previously studied normal subjects. The remaining seven subjects (Group 1) had blunted or absent natriuretic responses compared with that in normal subjects (p less than 0.005). Similar results were obtained with saline administration; cumulative Na excretion in Group 1 was markedly less than that in Group 2 and the normal subjects. The heterogeneity in Na excretion indicates that an exaggerated natriuresis is not a uniform concomitant of essential hypertension. The significant inverse correlation between basal plasma aldosterone level and peak urinary as well as cumulative Na excretion suggests that plasma aldosterone constitutes a determinant of the differing natriuretic responses. In contrast to findings with urinary Na excretion, the diuretic responses of Groups 1 and 2 were identical. The striking dissociation between renal Na and water handling underscores the specificity of the derangement in renal Na handling.

Adult↗
PubMed1986

The choice of an initial antihypertensive agent.

With the current availability of a plethora not only of blood pressure-lowering medications but also of classes thereof and the concern that the long-term use of some of these may result in adverse effects which may offset their benefits has come the recognition of the importance of the choice of an initial antihypertensive agent. Indeed, the initially chosen medication will often be taken for the longest time. The purpose of this review is to consider nine of the major factors permitting a rational choice of medication: antihypertensive efficacy, mechanism of action, safety, patient acceptance (quality of life), cost, numbers of doses per day, need for laboratory follow-up, potential interactions with other drugs, and additional salutary effects. The question of the role of nondiuretic monotherapy is, of necessity, an integral component of this discussion. Preliminary data indicate that the use of this approach with some of the newer agents, including converting enzyme inhibitors and calcium channel blockers, constitutes excellent therapy, at least in certain patients. Finally, because one of the new approaches to antihypertensive therapy is comprehensive risk management, the effect of medication on the lipid profile is considered in some detail.

Adrenergic beta-Antagonists↗
PubMed1986

Increases in circulating atrial natriuretic factor during immersion-induced central hypervolaemia in normal humans.

The role of atrial natriuretic factor (ANF) in modulating volume and circulatory homeostasis remains uncertain, and there has been as yet no systematic analysis of the factors promoting ANF release in humans. Since immersion in water to the neck provides a 'volume stimulus' identical to that induced by 2 litres of saline, without plasma compositional change, immersion to the neck was used to assess the ANF response to acute central blood-volume expansion. Using a radio-immunoassay that reliably detected ANF in human plasma extracts, more than 80% of plasma immunoreactive (ir) ANF was shown to elute as a single peak on reverse-phase high performance liquid chromatography, with a retention time identical to that of the synthetic 28-residue alpha-human (alpha-h) ANF. The response of plasma irANF to 3 h of immersion in water to the neck was evaluated in four sodium-replete normal subjects; the immersion produced a prompt and marked increase in irANF in each subject, and recovery was associated with a prompt return to pre-study levels. Concurrently, there was a marked natriuresis and a profound suppression of plasma renin and aldosterone. These findings support the hypothesis that an increase in plasma ANF contributes to the hormonal and renal effects of immersion in water to the neck, suggesting that ANF has an important physiological role in modulating volume homeostasis in humans.

Adult↗
PubMed1986

Continuous arterio-venous ultrafiltration in cirrhotic patients with ascites or renal failure.

To assess whether continuous arteriovenous ultrafiltration (CAVU) might constitute a useful alternative to hemodialysis in the management of patients with advanced liver failure, we carried out CAVU in 3 patients with decompensated Laennec's cirrhosis. CAVU was utilized in two patients with acute renal failure and pulmonary edema to stabilize renal function and facilitate administration of large amounts of fluid. In the third case, CAVU was successfully utilized to mobilize fluid in a patient refractory to conventional diuretic regimens. We conclude that CAVU may constitute an appropriate alternative to traditional hemodialysis in patients with advanced liver disease and renal functional impairment.

Aged↗
PubMed1986

Targeting antihypertensive therapy to the individual patient.

Currently, there are of a plethora not only of blood pressure-lowering medications but classes thereof. This massive armamentarium is a luxury, but has also raised appropriate concern that the long-term use of many of the agents may result in adverse effects that may offset their benefits. Because of this, the physician's choice of an initial antihypertensive agent has become even more important. Indeed, the initially chosen medication will often be taken for the longest time. The purpose of this review is to consider the major factors permitting a rational choice of medication, including demographic considerations such as race and age, coexisting diseases that commend one agent rather than another, safety, patient acceptance (quality of life), potential interactions with other drugs, and additional salutary effects. The question of the role of nondiuretic monotherapy is, of necessity, an integral component of this discussion. Preliminary data indicate that the use of this approach with some of the newer agents, including calcium channel blockers and converting enzyme inhibitors and blockers, constitutes excellent therapy in many patients. Finally, because of the new approaches to antihypertensive therapy in comprehensive risk management, the effect of medication on the metabolic and lipid profile are also considered.

Antihypertensive Agents↗
PubMed1985

Effects of atenolol on exercise capacity in patients with mitral stenosis with sinus rhythm.

Exercise capacity is frequently impaired in patients with mitral stenosis (MS) and sinus rhythm (SR). The resulting increased heart rate, which shortens the diastolic filling period, and the increased cardiac output lead to further elevations of left atrial pressure and subsequent pulmonary congestion. The effect of the beta-receptor blocking agent atenolol, 100 mg/day, was assessed in 13 patients with MS and SR. Exercise performance was assessed using a modified multistage Bruce protocol after 2 weeks of placebo and after 2 weeks therapy with atenolol in a single-blind, crossover, placebo-controlled, randomized study. Atenolol resulted in significant decreases in mean heart rates at rest and during exercise (p = 0.0015) and a significant increase in total exercise time (p = 0.0015). Maximal exercise capacity was also significantly improved (p = 0.0015). All patients were both objectively and subjectively improved by atenolol. Thus, beta-blockade with atenolol improves exercise capacity in patients with MS and SR and may be of benefit to most such patients. The improved effort tolerance is attributed to reduction of the exercise-associated sinus tachycardia by beta-blockade, allowing a longer diastolic filling period and better left atrial decompression.

Adolescent↗
PubMed1985

Derangements of renal water handling in liver disease.

It is apparent that renal water retention in patients with advanced liver disease constitutes a fascinating clinical constellation with numerous and diverse causes and an elusive pathophysiology. The dissociation between elevated AVP levels and the attendant changes in renal water handling under diverse experimental conditions, and the demonstration of an impairment in renal water excretion in response to prostaglandin synthetase inhibition, underscore the multifactorial nature of the derangement. It is likely that the development of impaired renal water handling is attributable to a panoply of several hormonal or neural mediators, or both, acting in concert. Additional insight into this fascinating problem must await further characterization of some of the mediators and a delineation of their pathophysiologic role.

Body Water↗
PubMed1985

Management of hydrocephalus in infancy: use of acetazolamide and furosemide to avoid cerebrospinal fluid shunts.

Despite its effectiveness, cerebrospinal shunting for hydrocephalus continues to be accompanied by considerable complications and morbidity. Medical therapy with acetazolamide 100 mg/kg/day and furosemide 1 mg/kg/day can be an effective alternative to shunting by halting progression of hydrocephalus until such time as sutures can become fibrosed and spontaneous arrest can occur. In an appropriately selected population older than 2 weeks with hydrocephalus of varied origin, our success rate in avoiding shunting is greater than 50%. The dramatic difference between the number of hospitalizations of patients with shunts and those treated medically, and the potential to avoid shunt dependence would appear to make an initial trial with medical therapy worthwhile.

Acetazolamide↗
PubMed1985

Effects of calcium antagonists on renal hemodynamics.

The renal hemodynamic effects of Ca2+ antagonists are considered in the context of their actions on Ca2+ movements during activation of vascular smooth muscle. Observations in intact animals reveal that the renal hemodynamic response to Ca2+ antagonists is highly variable, depending on the neural and hormonal determinants of renal vascular tone. Studies in the isolated perfused kidney and in isolated renal vessels indicate that diverse agonists use different activating mechanisms with differing sensitivities to Ca2+ antagonists. In comparison with other direct-acting vasodilators, Ca2+ antagonists are unique in their ability to maintain or increase glomerular filtration rate. This effect is due, in part, to their selective reduction of afferent arteriolar resistance. This implies that activating mechanisms of the afferent and efferent arterioles differ. The ability of Ca2+ antagonists to augment glomerular filtration rate by concomitant actions on nonvascular sites remains to be elucidated.

Animals↗