Search PubMed⌕ Search

Biomedical subjects

G M Eisner

Publications and source records attributed to G M Eisner.

At least 55 records · Page 3Linked to original sources
PubMed1988

Dopamine blockade attenuates the natriuresis of saline loading in the adrenalectomized rat.

Dopamine blockade with the dopamine-1/dopamine-2 antagonist cis-flupenthixol (CF) attenuates sodium excretion associated with saline loading in both innervated and denervated kidneys of the rat. Blockade of adrenal dopamine-2 receptors prevents the decrease in aldosterone secretion associated with saline loading and may also be responsible for the reduction in sodium excretion induced by CF. Therefore, to determine the role of adrenal dopamine-2 receptors in the attenuated natriuresis induced by CF, the effect of CF or vehicle treatment was examined in two groups of saline-loaded rats 80 (group I) and 120 min (group II) after adrenalectomy. In both groups, CF decreased glomerular filtration rate and sodium excretion after adrenalectomy. It is concluded that dopamine blockade attenuates the natriuresis associated with sodium loading by a direct effect in the kidney.

Adrenalectomy↗
PubMed1987

Renal hemodynamics and natriuresis induced by the dopamine-1 agonist, SKF 82526.

The intrarenal infusion of dopamine (DA) during alpha- and beta-adrenergic blockade has been reported to increase renal blood flow (RBF) and sodium excretion by occupation of DA-1 receptors. In addition, DA may potentially influence renal function by occupation of DA-2 receptor subtypes. This study was designed to examine the hemodynamic and/or tubular mechanisms of the natriuretic effect of DA-1 in dogs anesthetized with pentobarbital. The intrarenal infusion of the DA-1 agonist, SKF 82526 (10(-9), 10(-8), 10(-7) M), resulted in dose related increases in RBF and absolute and fractional sodium excretion. These changes were not associated with alterations in urinary prostaglandin E2, F2 alpha, or kallikrein excretion. To determine the role of RBF in the natriuresis due to SKF 82526 infusion (10(-7) M), the renal artery was constricted to return RBF to control levels during continued SKF 82526 infusion. Although absolute and fractional sodium excretion decreased during this maneuver, they remained higher than control. These studies support both a hemodynamic and a tubular mechanism for the natriuretic effect of the DA-1 agonist, SKF 82526. These effects do not appear to be mediated by the renal prostaglandin or kallikrein systems.

Animals↗
PubMed1986

Dopamine receptors modulate sodium excretion in denervated kidney.

Dopamine (DA) modulates sodium excretion by the innervated kidney. To examine the role of DA in the denervated (DNX) kidney the effects of the DA1/DA2 antagonist cis-flupenthixol (group 2, n = 7) (10 nmol X kg-1 X min-1), given intravenously in saline-loaded Wistar-Kyoto rats after acute unilateral left DNX, were compared with a placebo group (group 1, n = 7) and a group that received the DA1 antagonist SCH 23390 (group 3, n = 7) at 2.5 nmol X kg-1 X min-1. Pentobarbital sodium anesthesia was employed. Adequacy of DNX was assessed by a natriuresis and decrease in renal norepinephrine content in the DNX kidney and an antinatriuresis in the innervated right kidney. Mean arterial pressure slightly decreased in the placebo group (group 1, 106.7 +/- 2.2 vs. 99.3 +/- 2.4 mmHg) and after cis-flupenthixol (group 2, 108.8 +/- 2.7 vs. 92.8 +/- 1.8 mmHg) but not after SCH 23390 (group 3, 105.6 +/- 1.6 vs. 103 +/- 1.1 mmHg). Glomerular filtration rate was not affected by placebo or SCH 23390 in the DNX or innervated kidney but did slightly decrease after cis-flupenthixol in the DNX kidney. Sodium and water excretion after drug administration differed among the groups. In the DNX kidney urine flow decreased only in group 2, whereas fractional sodium excretion decreased modestly (P less than 0.05 paired t test) with SCH 23390 (3.53 +/- 0.34 vs. 2.89 +/- 0.20%) markedly with cis-flupenthixol (3.18 +/- 0.50 vs. 1.21 +/- 0.18%) and was unchanged in the placebo group (3.25 +/- 0.61 vs. 3.45 +/- 0.45%).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Renal alpha-adrenoceptors and sodium excretion in the dog.

The purpose of this study was to characterize the age-dependent role of alpha-adrenergic activity on renal vascular resistance (RVR) and renal blood flow (RBF) and the role of alpha 2-receptors in sodium transport. Intrarenal infusion of phentolamine in hydropenic anesthetized pups and adult dogs increased RBF and glomerular filtration rate (GFR) only in pups. The effect was most marked in the youngest pups (15.67 +/- 0.67 days). At 1.0 micrograms X kg-1 X min-1, phentolamine increased RBF from 1.38 +/- 0.04 to 1.64 +/- 0.04 ml X min-1 X g kidney wt-1 and GFR from 0.19 +/- 0.01 to 0.23 +/- 0.01 ml X min-1 X g kidney wt-1. Absolute (UNaV) and fractional (FENa) sodium excretions increased in all animals, but mean percent increases were greatest in adult dogs. Intrarenal yohimbine infusion in adult dogs (10-100 micrograms X kg-1 X min-1) produced a dose-related increase in UNaV and FENa without affecting RBF and GFR. UNaV increased from 0.22 +/- 0.05 to 0.54 +/- 0.12 mueq X min-1 X g kidney wt-1 and FENa increased from 0.32 +/- 0.05 to 0.63 +/- 0.06% at the dose of 100 micrograms X kg-1 X min-1. These studies confirm a modest role for alpha-adrenoreceptors in the high RVR characteristic of newborn pups and provide evidence for a role of alpha 2-adrenoceptors in the renal transport of sodium; the extent of the contribution of renal alpha-adrenergic system could not be tested in this experiment.

Animals↗
PubMed1984

Cortical tubular and glomerular dopamine receptors in the rat kidney.

Dopamine receptors in glomeruli and renal cortical tubules were characterized using radioligand binding and adenylate cyclase studies. The binding of [3H]haloperidol to glomeruli and tubules was rapid, saturable with time and ligand concentration, reversible, of high affinity, and demonstrated stereoselectivity and antagonist and agonist rank potency for binding to dopamine receptors. Analysis of kinetic data and Rosenthal plots in glomeruli revealed a single class of [3H]haloperidol binding sites with an apparent dissociation constant (Kd) of 6 nM and maximum receptor density (Bmax) of 0.42 pmol/mg protein. In tubules, at least two binding sites were noted, one with an apparent Kd of 38 nM and Bmax of 1.90 pmol/mg protein and another with an apparent Kd of 183 nM and Bmax of 3.50 pmol/mg protein. Dopamine and apomorphine increased adenylate cyclase in tubular membranes while no increases were noted in glomeruli. These studies suggest that glomeruli have D2 dopamine receptors, while renal cortical tubules contain the D1 dopamine receptor.

Adenylyl Cyclases↗
PubMed1983

Effects of dopamine blockade on renal sodium excretion.

The renal responses to a specific dopamine antagonist (cis-flupentixol) and its stereoisomer (trans-flupentixol), a weak dopamine antagonist, were examined during hydropenia and Ringer loading in anesthetized rats. During hydropenia glomerular filtration (GFR), absolute (UNaV), and fractional (FENa) sodium excretion rates were similar as were single-nephron filtration (SNGFR) and proximal tubular flow rate (VTF). After Ringer loading GFR, UNaV, and FENa increased in all groups, but the increments were less in the cis-flupentixol than in the control or trans-flupentixol group. SNGFR and VTF increased similarly in all groups. In another series of experiments Ringer loading was performed prior to drug administration. Perfusion pressure (PP) was decreased in trans-flupentixol rats by aortic constriction to control for cis-flupentixol-induced reduction in PP. UNAV and FENa were lower in the cis-flupentixol- than trans-flupentixol-treated rats at comparable PP and GFR. In conclusion, dopamine blockade attenuated the natriuresis of Ringer loading; the mechanism is uncertain but may be related to a tubular effect at a site beyond the proximal convoluted tubule and/or in deeper nephrons.

Animals↗
PubMed1983

Alpha-adrenoceptors in the developing kidney.

The maturation of renal alpha-adrenoceptors was investigated in dogs. Alpha-adrenoceptors were characterized by radioligand binding using the alpha-1-adrenergic antagonist, [3H]-WB-4101. In renal plasma membranes obtained from the outer cortex of neonates, the binding of the ligand was rapid, reversible, of high affinity, saturable, and stereoselective. The competition studies with adrenergic agonists and antagonists were indicative of alpha-receptors. In puppies less than 1-w-old, the binding affinity of [3H]-WB-4101 (Kd = 0.638 +/- 0.17 nM) was greater than 3-5 week-old puppies (Kd 1.573 +/- 0.315 nm); (P less than 0.05), but receptor number was similar (63.75 +/- 19.1 versus 79.10 +/- 5.99 fmole/mg protein). No consistent specific binding could be demonstrated in plasma membranes obtained from inner cortex of medulla. In the adult dog, no consistent specific binding could be demonstrated for plasma membranes obtained from any region of the kidney. These studies indicate that during maturation there is a decrease in alpha-adrenoceptor density and affinity in membranes from the outer cortex of the kidney.

Adrenergic alpha-Antagonists↗
PubMed1983

The influence of age on acute renal toxicity of uranyl nitrate in the dog.

The influence of age upon uranyl nitrate (UN) induced acute renal failure (ARF) was evaluated in 30 canine puppies 1-2 wk and 3-5 wk old. Renal function and morphologic studies were performed 2 h (initiation phase) and 24 h (maintenance phase) after UN administration. Age-matched controls received vehicle alone. Administration of UN to 1-2-wk-old puppies produced no changes in whole kidney glomerular filtration rate (GFR), despite a significant reduction in renal plasma flow (RPF) (P less than 0.01). In contrast, during the maintenance phase, GFR was 60% lower than in the control group (P less than 0.02) whereas values for RPF were nearly identical to control values. In 3-5-wk-old puppies the magnitude of response to the heavy metal was much greater and GFR was nearly completely suppressed during the maintenance phase. This major alteration of GFR was independent of changes in RPF, because RPF remained similar to control values. Morphologic alterations consistent with the nephrotoxic effects of UN were observed in the proximal tubules of the most differentiated nephrons. These age-related morphologic alterations correlated well with the functional response (GFR) observed after UN administration, i.e., a proportionately greater degree of both morphologic and functional alterations followed the administration of the heavy metal in the oldest group of puppies.

Acute Kidney Injury↗
PubMed1982

Cyclic nucleotide response to stimulation in isolated glomeruli from dog kidney.

The effects of biogenic amines on cyclic 3',5'-adenosine monophosphate (cAMP) and on cyclic 3',5'-guanosine monophosphate (cGMP) were studied in isolated glomeruli from dog kidneys. Of the agents tested, histamine produced the greatest increase in cyclic nucleotide activity. Isoproterenol, dopamine, epinephrine and norepinephrine also produced increases in cAMP and/or cGMP activity but of lesser magnitude. Propranolol decreased cyclic nucleotide levels. Glomeruli isolated from the outer cortex showed greater responses to stimulation than glomeruli from the inner cortex.

Animals↗
PubMed1982

Ontogeny of myocardial adrenoceptors II. Alpha adrenoceptors.

The maturation of myocardial alpha adrenoceptors was investigated in dogs. Alpha adrenoceptors were characterized by radioligand binding using [3H]-WB4101. In neonatal cardiac membranes, the binding of the ligand was rapid, reversible, of high affinity, saturable and stereoselective. The competition studies with adrenergic agonists and antagonists were indicative of alpha adrenoceptors. In adult dog cardiac membranes, consistent specific binding of the ligand could be demonstrated. These studies indicate that there is a decrease in alpha adrenergic receptor density of canine cardiac membranes during maturation.

Adrenergic alpha-Agonists↗
PubMed1982

The role of anesthesia and catecholamines in the renal response to mild hemorrhage.

The role of the sympathoadrenal system in the renal response to mild hemorrhage was investigated in animals anesthetized with either sodium pentobarbital (Group I) or alpha-chloralose (Group II). Significantly greater decreases in renal blood flow (RBF) and increases in renal vascular resistance (RVR) were seen after hemorrhage in Group II than in Group I. Concomitant with these changes were increases both in circulating catecholamines and plasma renin activities. In Group II, however, the rise in plasma epinephrine was also significantly higher than in Group I. Additional studies were performed in pentobarbital anesthetized dogs either chemically denervated with 6-hydroxydopamine (Group III) or treated with the prostaglandin synthetase inhibitor indomethacin (Group IV). In Group III, following hemorrhage, changes in renal hemodynamics and circulating catecholamines were similar to those of Group I. In Group IV, although blood pressure was better maintained during hemorrhage than in the other groups, RVR increased to the same extent as in Group II, although increases in circulating catecholamines were comparable to those observed in Group I. Whereas pentobarbital anesthesia attenuated the sympathoadrenal response to mild hemorrhage, indomethacin appeared to sensitize the animals to adrenergic discharge by removing the modulatory effect of the prostaglandin system.

Anesthetics↗