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Biomedical subjects

I Seri

Publications and source records attributed to I Seri.

At least 37 records · Page 2Linked to original sources
PubMed1993

Effects of low-dose dopamine infusion on cardiovascular and renal functions, cerebral blood flow, and plasma catecholamine levels in sick preterm neonates.

Effects of 2 and 4 micrograms/kg/min dopamine infusion on cardiovascular and renal functions, cerebral blood flow (CBF) and plasma catecholamine levels were studied in sick preterm neonates during the first four days of life. Preterm infants were found to have an enhanced responsiveness to the pressor effects of dopamine during this period. Comparison of the renal effects of 2 and 4 micrograms/kg/min dopamine in 61 preterm infants indicate that 2 micrograms/kg/min dopamine induces maximum diuresis and natriuresis during the first day of life provided that systemic blood pressure is within the predicted normal range. Although administration of 4 micrograms/kg/min dopamine induces further increases in blood pressure and glomerular filtration rate, urine output and sodium excretion remain similar to that on 2 micrograms/kg/min of the drug. These findings demonstrate that the direct tubular effects of dopamine play an important role in the diuretic and natriuretic action of the drug in the one-day old preterm infant. In five preterm neonates, changes in CBF transiently paralleled the dopamine-induced alterations in systemic blood pressure indicating that autoregulation of CBF is impaired but not completely ineffective in the one-day old preterm infant. In eight term neonates, increases in blood pressure had no effect on CBF. Measurements of plasma dopamine and norepinephrine levels in 14 preterm neonates and five children suggest that decreased metabolism of dopamine may contribute to the enhanced pressor responsiveness to dopamine in sick preterm infants.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure↗
PubMed1990

The significance of L-amino acid decarboxylase and DARPP-32 in the kidney.

This study examines the role of endogenous dopamine (DA) for the regulation of renal tubular sodium (Na) transport. The enzyme L-amino acid decarboxylase (L-AADC) that converts L-dopa to DA has been localized to the proximal tubule cells with immunocytochemistry. Locally formed DA will inhibit the activity of Na-K-ATPase, the enzyme that yields energy to active Na transport. The effect is of physiological importance during high salt diet. The phosphoprotein DARPP-32, a DA1 receptor associated third messenger is abundant in the medullary thick ascending limb of Henle (mTAL). DARPP-32 is phosphorylated after activation of DA1 receptors. DARPP-32 is in its phosphorylated form a potent phosphatase inhibitor. Activation of the DA1 receptor in mTAL with the DA1 agonist SKF 82526 causes dose-dependent inhibition of Na-K-ATPase activity. The effect involves activation of cAMP protein kinase. It is likely that this effect is potentiated by DARPP-32.

Animals↗
PubMed1990

Influence of Na+ intake on dopamine-induced inhibition of renal cortical Na(+)-K(+)-ATPase.

The enzyme L-amino acid decarboxylase (L-AADC), found in abundance in rat proximal tubule cell cytosol, converts L-dopa to dopamine. Dopamine, in turn, suppresses proximal tubule sodium transport by inhibiting Na(+)-K(+)-ATPase activity. We sought to determine whether changes in dietary sodium intake in rats lead to adaptation of dopamine formation and dopamine-induced Na(+)-K(+)-ATPase inhibition. In rats on a high-salt (HS) diet, the maximal velocity (Vmax) of renal cortical L-AADC was 78 +/- 19% higher than that in rats on a low-salt (LS) diet. The Michaelis constant (Km) of the enzyme remained unchanged. In renal cortical tubule cell suspensions the L-dopa-induced inhibition of ouabain-sensitive oxygen consumption (QO2) was significantly greater in rats on HS diet than in rats on LS diet. Furthermore, L-dopa completely inhibited the nystatin-induced rise in QO2 in the HS but not in the LS group. Carbidopa, an inhibitor of L-AADC, abolished the L-dopa-induced inhibition of nystatin-stimulated QO2 in cells from HS rats and was without significant effect in cells from LS rats. L-Dopa-stimulated K+ efflux was greater in cells from HS rats at 28 +/- 1 nmol.min-1.mg protein-1, compared with 7 +/- 6 nmol.min-1.ng protein-1 in cells from LS rats. By contrast, ouabain-stimulated K+ efflux did not differ between the groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Dopamine1-receptor blockade inhibits ANP-induced phosphaturia and calciuria in rats.

Atrial natriuretic peptide (ANP) is known to enhance the excretion of Pi and Ca, solutes reabsorbed primarily by the proximal tubule. Previous studies have shown that proximal tubule Na transport is inhibited by dopamine (DA), and that the natriuretic action of ANP is blunted by DA-receptor blockade. However, alterations in Na reabsorption cannot localize ANP or DA action to a specific nephron site. Therefore, the possibility that DA mediates the apparent proximal tubule effects of ANP was investigated with the use of Pi and Ca as proximal tubule markers. ANP was infused into normal rats in the presence and absence of specific DA-receptor antagonists, and Na, Pi, and Ca excretion rates were determined. ANP enhanced Na, Pi, and Ca excretion at doses that failed to alter glomerular filtration rate and mean arterial pressure (MAP). DA1-receptor blockade significantly blunted the influence of ANP on urinary Na, Pi, and Ca excretion, whereas DA2-receptor blockade was without effect. MAP and inulin and p-aminohippurate (PAH) clearances remained stable during DA-receptor blockade. Because endogenous ANP levels are elevated in rats with remnant kidneys, and because blockade of endogenous ANP reduces Pi and Ca as well as Na excretion in this model, the effect of DA1-receptor blockade on solute excretion was also examined in rats with 5/6 nephrectomy. DA1-receptor blockade significantly reduced absolute and fractional Na, Pi, and Ca excretion in rats with 5/6 nephrectomy, in the absence of measurable changes in MAP, inulin, or PAH clearance.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Dopamine and natriuresis. Mechanism of action and developmental aspects.

The present paper summarizes our studies on the mechanisms of the dopamine induced changes in renal macro- and microcirculation as well as in proximal and distal tubular sodium handling which contributes to the natriuresis induced by the drug. Some aspects of the physiological role of locally generated dopamine in regulating sodium excretion are also reviewed. Finally, by describing the cardiovascular, renal and hormonal effects of dopamine in the preterm human neonate, some of the developmental aspects of the renal effects of the drug are also discussed.

Animals↗
PubMed1989

Glomerular adaptation in uninephrectomized young rats.

To study the glomerular adaptation during compensatory renal growth starting in infancy, we assessed afferent effective ultrafiltration pressure (PUF), glomerular filtration area and hydraulic conductivity in rats uninephrectomized (Nx) or sham-operated (S) at 5 days of age. Rats were fed a normal protein diet and studied at 20 and 60 days of age. Single nephron glomerular filtration rate was significantly higher in Nx than in S rats both at 20 days of age (mean +/- SEM: 15.0 +/- 1.5 vs 7.4 +/- 0.7 nl/min) and 60 days of age (80.7 +/- 4.6 vs 43.5 +/- 3.2 nl/min). Afferent effective PUF, estimated by the stop-flow method, was significantly higher in Nx than in S rats both at 20 days (22.5 +/- 0.8 vs 18.3 +/- 0.4 mmHg) and 60 days (28.3 +/- 1.0 vs 23.2 +/- 1.1 mmHg). The filtering area per glomerulus, calculated as the area of the glomerular basement membrane facing both the endothelial and the epithelial cells, but not the mesangial cells, was not different in Nx and in S rats at 20 days (3.0 +/- 0.3 vs 2.8 +/- 0.1 10(4) microns 2), but it was significantly greater in Nx than in S rats at 60 days (23.3 +/- 3.7 vs 9.9 +/- 0.9 10(4) microns 2). The hydraulic conductivity determined in isolated glomeruli was similar in Nx and in S rats at 20 days of age (1.40 +/- 0.11 vs 1.69 +/- 0.23 microliters/min.mmHg.cm2) but was significantly decreased in 60-day-old Nx rats, compared with S rats of the same age (1.52 +/- 0.11 vs 2.35 +/- 0.17 microliters/min.mmHg.cm2).(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗
PubMed1988

Effect of low-dose dopamine infusion on urinary prostaglandin E2 excretion in sick, preterm infants.

In pharmacological doses dopamine (DA) will interact with several endocrine systems and both inhibit (prolactin, thyrotropin) and enhance (renin, angiotensin) hormonal release. In this study we have examined whether DA given to preterm neonates will influence prostaglandin (PG) production. The question is of importance since vasodilator PGs play a role in postnatal adaptation. We determined the effect of low dose DA infusion on the 24 h urinary PGE2 excretion rate (an index of renal PGE2 synthesis) in preterm infants. Six preterm neonates, with a 24-h requirement of 2 micrograms/kg per min DA treatment for oedema, moderate oliguria, poor peripheral perfusion and/or mild systemic hypotension were studied on days 2 (Day 1), 3 (Day 2, the day of DA infusion), and 4 (Day 3, DA discontinued) of life. Six preterm infants (control group) that did not require DA infusion were also studied to monitor possible spontaneous changes in the renal PGE2 production on days 2, 3 and 4 of life. In the control group urine output (Uv) and PGE2 excretion rate remained unchanged during the study. In the study group DA administration resulted in nearly two-fold increases in both the Uv (194%) and PGE2 excretion (182%). Urinary PGE2 excretion was, however, closely related to urine flow in both the control infants (Day 1-3) and the study group infants (Day 1-2). Since increased diuresis stimulates renal PGE2 production, our data suggest that the increased PGE2 excretion on Day 2 in the study group was not due to a direct effect of DA on PGE2 synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Dinoprostone↗
PubMed1988

Contribution of dopamine 2 receptors to dopamine-induced increase in glomerular filtration rate.

The effects of the interaction of dopamine (DA) and the DA2 receptors on glomerular filtration rate (GFR) has been studied by means of micropuncture technique in adult greater than or equal to 60-day-old and young 24-day-old rats. Most of the studies were performed in rats with intact adrenergic nervous systems to allow for evaluation of the presynaptic DA2 receptors. In adult and young rats, DA and LY-171555 (LY), a selective DA2 receptor agonist, induced prompt and significant increases in the single nephron (SN) GFR. Further studies were performed only in adult rats. The LY-induced increase in SNGFR was completely abolished during DA2 receptor blockade with S-sulpiride (S-SP), while the DA-induced increase in SNGFR was attenuated but still significant during S-SP treatment. Both DA and LY significantly increased the glomerular ultra-filtration pressure (PUFAA). In rats with ganglionic blockade, the LY-induced increase of SNGFR was attenuated but still significant, whereas the DA-induced increase was less affected. The results imply that DA significantly increases GFR by interacting with the DA2 as well as with the DA1 receptors. Interaction between DA and the DA2 receptors increases PUFAA. The results do not rule out the existence of both pre- and postsynaptic renal DA2 receptors.

Animals↗
PubMed1988

Locally formed dopamine inhibits Na+-K+-ATPase activity in rat renal cortical tubule cells.

Dopamine, generated locally from L-dopa, inhibits Na+-K+-ATPase in permeabilized rat proximal tubules under maximum transport rate conditions for sodium. To determine whether locally formed dopamine inhibits Na+-K+-ATPase activity in intact cortical tubule cells we studied the effect of L-dopa on ouabain-sensitive oxygen consumption rate (QO2) and 86Rb uptake in renal cortical tubule cell suspensions. L-Dopa (10(-4) M) did not affect ouabain-insensitive QO2 or mitochondrial respiration. However, L-dopa inhibited ouabain-sensitive QO2 in a concentration-dependent manner, with half-maximal inhibition (K0.5) of 5 x 10(-7) M and a maximal inhibition of 14.1 +/- 1.5% at 10(-4) M (P less than 0.05). L-Dopa also blunted the nystatin-stimulated QO2 in a concentration-dependent manner, with a K0.5 of 5 x 10(-8) M and a maximal inhibition of 21.8 +/- 1.2% at 10(-5) M (P less than 0.05), indicating that L-dopa directly inhibits Na+-K+-ATPase activity and not sodium entry. Ouabain-sensitive 86Rb uptake was also inhibited by L-dopa (16.0 +/- 2.4%, P less than 0.05). Carbidopa (10(-4) M), an inhibitor of the conversion of L-dopa to dopamine, eliminated the effect of L-dopa on ouabain-sensitive QO2 and 86Rb uptake, indicating that dopamine rather than L-dopa was the active agent. The finding that the L-dopa concentration-response curve was shifted to the left by one order of magnitude in the presence of nystatin suggests that the inhibitory effect is enhanced when the intracellular sodium concentration is increased.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Influence of dopamine on atrial natriuretic peptide level in premature infants.

The role of dopamine (DA) in the activation and/or release of atrial natriuretic peptide (ANP) was investigated in 11 premature infants during the early postnatal period. Mean plasma concentration of ANP and free DA level before DA infusion was 252.6 +/- 210 fmol/ml, and 0.4 +/- 0.2 ng/ml, respectively. DA infusion in a dose of 2 micrograms/kg/min caused a rise in plasma free DA level to 59.7 +/- 21.5 ng/ml and a significant increase in GFR, diuresis, sodium excretion and fractional sodium excretion. The plasma concentration of ANP, however, remained unchanged (252.6 +/- 210.0 vs. 213 +/- 143.0 fmol/ml). Thus, our data failed to demonstrate a stimulatory effect of DA on ANP release in premature infants. The role of the high plasma concentration of ANP in preterm neonates immediately after birth has to be clarified.

Atrial Natriuretic Factor↗
PubMed1987

Atrial natriuretic peptide and extracellular volume contraction after birth.

Plasma concentrations of atrial natriuretic peptide (ANP) were measured in full-term newborns immediately after birth and on the 3rd, 5th, 7th and 10th day of life. The ANP concentrations were within the normal range in the first hours of life. Plasma concentrations of ANP had increased significantly on the 3rd and 5th day of life, while body weight decreased continuously. After the 5th day of life ANP concentration decreased continuously reaching its minimum on the 10th day whereas body weight increased. The mechanism behind ANP release shortly after birth is not known. The increase in ANP concentration in plasma may however induce changes in body fluid compartments shortly after birth which would result in physiological weight loss.

Age Factors↗
PubMed1987

Role of dopamine2-receptors in mediating renal vascular response to low dose dopamine infusion in the rat.

The effects of the interaction of dopamine (DA) and the DA2-receptors on regional blood flows and cardiac output have been studied in the rat. By means of the microsphere technique the blood flow (BF) and vascular resistance (VR) were determined in the kidney, duodenum, spleen, liver, and lung during infusion of DA in the absence and presence of selective DA2-receptor blockade with S-Sulpiride (S-SP), and during infusion of a selective DA2-receptor agonist (LY-171555, LY). In order to evaluate the role of the presynaptic DA2-receptor, the experiments were performed without alpha- and beta-adrenergic blockade. Dopamine was given in such low doses that stimulation of the adrenergic receptors should be negligible. Dopamine, LY and DA + S-SP did not significantly influence BF and VR in the spleen, liver and lung. Dopamine significantly increased BF and decreased VR in the kidney and the duodenum; LY significantly increased BF in the the kidney but not in the duodenum and decreased VR in both the kidney and the duodenum. In the presence of selective DA2-receptor blockade, DA did not significantly influence BF or VR in the kidney but in the duodenum BF increased and VR decreased to the same extent as in the absence of blockade. In conclusion; the kidney and the intestine are more abundantly supplied with vascular DA-receptors than other organs. In the kidney the interaction between DA and the DA2-receptors significantly contributes the the DA-induced vasodilation. The interaction between DA and the DA2-receptors is of less importance for the DA-induced vasodilation in the intestine.

Animals↗
PubMed1987

Dopamine causes inhibition of Na+-K+-ATPase activity in rat proximal convoluted tubule segments.

We studied the effect of dopamine (DA) on Na+-K+-ATPase activity in proximal convoluted tubule (PCT) segments dissected from perfused rat kidneys. DA inhibited Na+-K+-ATPase activity in a dose-dependent manner. Inhibition was significant with 10(-7) M DA and maximal with 10(-4) M DA. The inhibition was reversible. Enzyme inhibition occurred in the presence of DA and a DA antagonist, metoclopramide, but not when 10(5) M of the DA1 and DA2 agonists fenoldopam mesylate and LY 171555 were added in the absence of DA. In PCT segments incubated with the DA precursor dopa, Na+-K+-ATPase activity was also inhibited. However, dopa did not inhibit the sodium pump if dopa decarboxylase activity was blocked with benserazide. These findings suggest an intracellular site of action of DA. In tubules incubated in different K concentrations, 10(-5) DA decreased the maximal activity (Vmax) and increased the Km. DA 10(-5) M caused an almost immediate swelling of PCT segments. Swelling did not occur in the presence of both DA and 10(-5) M amiloride. The DA-induced tubular swelling was probably due to inhibition of Na+-K+-ATPase-mediated Na+-transport. We conclude that in rat PCT segments, DA causes a rapid and reversible inhibition of apparent Na+-K+-ATPase activity and an apparent reduction in the affinity for K. The site of action appears to be intracellular.

Adenosine Triphosphatases↗