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Biomedical subjects

M Awazu

Publications and source records attributed to M Awazu.

36 records · Page 2Linked to original sources
PubMed1994

Alterations in renal function in experimental congestive heart failure.

The delicate interplay between vasoconstrictors and vasodilators preserves glomerular filtration in CHF despite marked hypoperfusion. Activation of vasoconstrictive systems seems to depend on the severity and the chronicity of the disease. The importance of renin-angiotensin, sympathetic nerves, vasopressin and counterregulatory ANP, and prostaglandins in CHF has been elucidated. Possible roles of newly identified substances, such as endothelin and EDRF, deserve investigation.

Animals↗
PubMed1993

Maintenance of endothelin-induced renal arteriolar constriction in rats is cyclooxygenase dependent.

Influence of arachidonate cyclooxygenase (COX) products on endothelin (ET)-evoked renal vasoconstriction was assessed. In microperfused rat afferent (AA) and efferent arterioles (EA), indomethacin had no effects on the maximal contraction of both AA and EA by ET, but reduced the duration of ET-induced constriction in both arterioles. ET infusion to rats in vivo resulted in a selective increase in efferent but not afferent arteriolar resistance, leading to a dramatic increase in transcapillary hydraulic pressure difference. Glomerular filtration rate (GFR), which fell progressively during infusion of ET alone, was markedly preserved by COX inhibition, but not during selective thromboxane A2 antagonism. In isolated glomeruli, release of prostaglandin (PG) F2 alpha in response to 10(-6) mol/l ET exceeded that the PGE2 by a ratio of 3.2. Collectively, these data provide strong evidence that locally released COX products, possibly PGF2 alpha, play a key role in sustaining ET-induced renal arteriolar constriction. COX inhibition leads to acute vasorelaxation of AA despite continued ET administration, without affecting EA constriction in vivo, thereby resulting in a dramatic reversal of the effects of ET on GFR.

Animals↗
PubMed1993

Biological significance of atrial natriuretic peptide in the kidney.

In summary, ANP exerts its action in the kidney directly and indirectly. Its qualitative importance in body fluid regulation remains unsettled. It appears that its role is more important in pathophysiological conditions such as CHF in which plasma ANP is elevated. Paradoxically, kidneys in heart failure, nephrosis and diabetes are characterized by diminished responsiveness to exogenous ANP. Further studies are needed to ascertain whether this involves an alteration at the receptor or postreceptor site. The cellular mechanisms for receptor regulation and postreceptor signalling in physiology and pathophysiology need further investigation. Finally, a paracrine mode for the action of ANP and other natriuretic peptides has been proposed. Whether they act locally to facilitate sodium excretion and how much importance they have compared to circulating ANP remain to be clarified. The potential role of ANP as a growth inhibitor is also intriguing.

Atrial Natriuretic Factor↗
PubMed1992

Dietary fatty acid modulates glomerular atrial natriuretic peptide receptor.

Modification of dietary fatty acid (FA) has been shown to affect the incidence of hypertension and coronary artery disease. We studied whether these effects involve changes in the receptor characteristics of vasoactive substance. Characteristics of atrial natriuretic peptide (ANP) receptors were examined in glomeruli isolated from rats fed a diet containing 5% in weight omega 6, 5% omega 3, 20% omega 6, 20% omega 3 polyunsaturated FA or 20% saturated FA (SFA) for greater than 4 weeks. The FA composition of phospholipids in isolated glomeruli showed an elevation in 20:4 omega 6 (arachidonic acid, AA) in 5% omega 6, 20% omega 6 and 20% SFA, and elevations in 20:5 omega 3 (eicosapentaenoic acid, EPA) in 5% omega 3 and 20% omega 3 groups. The radioligand binding study revealed: (1) in 20% FA group, receptor density (Ro, fmol/mg prot) of ANP was significantly decreased compared to 5% group (262 +/- 13, n = 8 to 120 +/- 13, n = 12) without changes in equilibrium dissociation constant (KD), (2) among high FA (20%) groups, type of FA was essential for determining Ro; higher omega 6 was associated with a lower ANP Ro (177 +/- 11 vs. 103 +/- 3 fmol/mg prot, P less than 0.05) and KD (0.43 +/- .04 vs. 0.27 +/- .02 nM, P less than 0.05). To examine whether the alteration in receptor characteristics is mediated by FA, effects of FA were examined in vitro. In cultured mesangial cells, AA, but not EPA, decreased Ro of ANP receptors (48.7 +/- 4.8% of control, P less than 0.05) without affecting KD.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Endothelin and cyclosporine nephrotoxicity.

Although some humoral and neural factors have been implicated in the persistent vasoconstriction characterizing many forms of acute renal failure, the mechanisms for this abnormal vascular function have remained largely unresolved. Several factors previously postulated to have a role in acute renal failure have been shown to enhance endothelin (Et) production or gene expression. We studied the potential pathophysiologic role for Et in several models of acute renal failure, including postischemia, endotoxin, and cyclosporine (Cy) nephrotoxicity. We have found that, in vivo, Cy (and also endotoxin) elevates circulating Et. We further showed that antagonizing Et's action with Et antibody ameliorates renal vasoconstriction following renal ischemia, Cy, and endotoxin administration. Additionally, our studies showed that even after circulating levels of Et decrease (following Cy), there is upregulation in Et receptors in the kidneys. Overall, endothelin appears to feature prominently in the pathophysiologic processes occurring during several forms of acute renal failure.

Acute Kidney Injury↗
PubMed1991

Down-regulation of endothelin-1 receptors by protein kinase C in streptozotocin diabetic rats.

The vasoconstrictor response is defective in diabetes mellitus (DM). Activation of protein kinase C (PKC) is also known to prevail in diabetes mellitus, and it is thought to be secondary to abnormal diacylglycerol metabolism. To ascertain whether this PKC activation in diabetes underlies the vasomotor defect by regulating biological receptors, we studied the characteristics of the receptor for endothelin (ET), "the vasoconstrictor of injury." For this purpose, diabetes was induced in rats by intravenous streptozotocin. One to 2 weeks after streptozotocin treatment (average glucose at time of experiments: 518 mg/dl), glomeruli were isolated and assessed for ET receptor and PKC activity. ET receptor characteristics were also assessed following infusion of a specific PKC inhibitor, 1-(5-isoquinolinesulfonyl)piperazine (CI). For comparison, nondiabetic controls with and without PKC inhibitor were studied. No differences in high-affinity ET-1 receptor (ER-1) characteristics were found among the diabetic and normal rats. In contrast, receptor density for the lower-affinity receptor (ER-2) was significantly depressed in DM without changes in the equilibrium dissociation constant. Infusion of CI 20 min before glomerular harvesting did not affect the glomerular PKC activity in controls (particulate: 28.0 +/- 4.0% of total activity to 22.0 +/- 3.9%, n = 3). In contrast, in diabetes mellitus rats infused with CI, PKC activity decreased (particulate: from 44.7 +/- 2.9% of total activity to 18.5 +/- 3.2%, n = 3, p less than 0.05). This CI-induced suppression of PKC in DM was accompanied by complete reversal in down-regulation of ER-2 receptors. Thus, DM is characterized by down-regulation in low-affinity ET-1 receptors. Furthermore, this receptor down-regulation can be reversed by abolishing abnormally enhanced PKC activity. These results indicate that abnormal activation of PKC may underlie the profoundly vasodilative status and defective vasoconstrictor response characterizing DM.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1991

Renal sympathetic nerves modulate glomerular ANP receptors and filtration.

We examined characteristics of atrial natriuretic peptide (ANP) receptors in glomeruli isolated from subacutely (3-5 days) denervated (DNX) and contralateral nondenervated (non-DNX) kidneys of normal rats (NL) and rats subjected to water deprivation for 48 h (WD). Total ANP receptor density in DNX kidneys of WD rats, measured by competitive inhibition binding between 125I-labeled ANP and ANP, was twofold higher than non-DNX kidneys (726 +/- 96 vs. 384 +/- 32 fmol/mg protein, P less than 0.05). Equilibrium association constant (Ka) was not significantly different (2.33 +/- 0.43 vs. 3.34 +/- 0.78 x 10(9) M-1). In NL rats, there was no difference in ANP receptor density between DNX and non-DNX kidneys (244 +/- 20 and 264 +/- 16 fmol/mg protein). Production of guanosine 3',5'-cyclic monophosphate (cGMP), a putative second messenger of ANP, in response to ANP (10(-7) M) in glomeruli isolated from DNX was significantly larger than non-DNX kidneys of WD rats. To determine whether these changes in ANP receptors have functional consequences in vivo, glomerular capillary ultrafiltration coefficient (Kf) was assessed by micropuncture technique in WD Munich-Wistar rats. In DNX kidneys, ANP infusion (4 micrograms.kg-1.h-1) significantly increased whole kidney glomerular filtration rate (GFR) and single-nephron (SN) GFR (0.64 +/- 0.06 to 0.89 +/- 0.17 ml/min and 25 +/- 2 to 33 +/- 2 nl/min, respectively; n = 7) and Kf (1.26 +/- 0.29 to 2.18 +/- 0.41 nl.min-1.mmHg-1).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Cyclosporine promotes glomerular endothelin binding in vivo.

It has previously been shown that administration of cyclosporine causes a prompt (within 15 min after infusion) increase in circulating level of endothelin 1 and a pattern of glomerular hypoperfusion and hypofiltration which can be ameliorated with antiendothelin antibody. We now show that 60 min after cyclosporine, serum endothelin 1 level falls to less than 2.55 +/- 0.31 pg/mL (N = 6), a value comparable to that found in normal animals (less than 2 pg/mL). The study presented here also examines whether sustained cyclosporine-induced glomerular dysfunction is associated with altered endothelin receptor characteristics. Saturation and competitive inhibition binding studies in isolated glomerular membranes showed two binding sites. Of these, the density of the low-affinity site was affected by cyclosporine treatment (851 +/- 117 versus 425 +/- 61 fmol/mg of protein; P less than 0.05; N = 6) without a change in equilibrium dissociation constant, KD. The high-affinity site was not affected. The receptor characteristics of another vasoconstrictor, angiotensin II, were not affected by cyclosporine. In addition, there was no difference in endothelin binding sites in hepatic tissue between cyclosporine and control rats. These results raise the intriguing possibility that cyclosporine-induced glomerular dysfunction involves upregulation of endothelin binding sites and that altered endothelin receptors appear specific to the kidney.

Animals↗
PubMed1989

Role of endogenous atrial natriuretic peptide in congestive heart failure.

Effects of purified rabbit anti-rat 25-amino acid atrial natriuretic peptide (ANP) immunoglobulin G (IgG) on renal sodium excretion and glomerular filtration rate were studied in a rat model of congestive heart failure (CHF) having high circulating ANP levels. Bolus injection of anti-ANP into anesthetized rats with surgically induced myocardial infarction (MI) significantly and markedly depressed both absolute and fractional urinary excretion of sodium without affecting mean arterial pressure or glomerular filtration rate. By contrast, anti-ANP failed to affect these renal functions in normal or acutely water-deprived rats. Nonimmune IgG did not affect renal function in MI rats. These results indicate that high circulating ANP plays an important role in sodium homeostasis of congestive heart failure: by promoting sodium excretion, ANP opposes the tendency of sodium retention characteristic of CHF.

Animals↗
PubMed1989

Blunted pressure natriuresis in the Brattleboro diabetes insipidus rat.

Antidiuretic hormone is known to stimulate the renal synthesis of prostaglandins. These autacoids, in turn, modulate the pressure natriuresis phenomenon. Accordingly, the present study was done to test the hypothesis that, in the absence of antidiuretic hormone and antidiuretic hormone-dependent prostaglandin synthesis, the pressure natriuresis response is blunted. Experiments were performed on Brattleboro diabetes insipidus rats (n = 7) and Long Evans control rats (n = 14). A change in perfusion pressure in the Long Evans rats from 89.3 +/- 1.0 to 108.7 +/- 1.1 mm Hg (p less than 0.05) was associated with significant increases in the fractional excretion of sodium (1.1 +/- 0.2 to 2.3 +/- 0.3%) and the urinary prostaglandin excretion (32.6 +/- 6.8 to 56.6 +/- 10.0 pg/min). In contrast, a similar change in perfusion pressure in the diabetes insipidus rat from 88.6 +/- 1.4 to 106.2 +/- 1.5 mm Hg (p less than 0.05) resulted in no significant increases in either sodium or prostaglandin excretions. Treatment of a third group of diabetes insipidus rats (n = 9) with 1-desamino-8-D-arginine vasopressin (1 microgram/day) restored the natriuretic response to increases in renal perfusion pressure. Treated diabetes insipidus and Long Evans control rats had comparable natriuretic responses to increases in renal perfusion pressure. Untreated diabetes insipidus rats, on the other hand, had blunted responses. In summary, the pressure natriuresis response in diabetes insipidus rats is blunted compared with Long Evans control rats. We conclude that antidiuretic hormone is necessary for the complete expression of the pressure natriuresis response.

Animals↗
PubMed1988

Natriuretic effect of atrial natriuretic peptide in diabetes insipidus rats.

Washout of the solute concentration gradient in the renal medullary interstitium has been suggested to play a role in mediating the natriuretic response to atrial natriuretic peptide (ANP). The purpose of this study was to determine the effects of ANP 8-33 on sodium excretion in Brattleboro diabetes insipidus (DI) rats, in which medullary tonicity is known to be decreased as compared to Long-Evans (LE) control rats. Basal urine osmolality (Uosm) was significantly lower in DI rats as compared to LE rats (123 +/- 6 vs 673 +/- 38 mOsm/kg). Infusion of ANP 8-33 at a rate of 4 micrograms/kg/hr for 60 min resulted in a significantly greater increase in UnaV (delta 6.1 +/- 1.2 vs delta 2.9 +/- 0.7 microEq/min) and urine flow (delta 40 +/- 12 vs delta 8 +/- 7 microliter/min) in the LE rats than in the DI rats. The greater natriuresis occurred in the LE rats despite no significant change in Uosm. Fractional lithium reabsorption (an indicator of proximal sodium reabsorption) decreased similarly in both groups. Infusion of ANP had no effect on mean arterial pressure in LE and DI groups. In summary, infusion of ANP in the DI rat resulted in a significant natriuresis, albeit less than in LE rats. The natriuresis in the LE rats occurred despite no significant change in Uosm. These data suggest that mechanisms other than medullary washout are responsible for the natriuretic effects of ANP.

Animals↗
PubMed1987

Effect of phosphate infusion on proximal tubule phosphate reabsorption in phosphate-deprived and respiratory alkalotic rats.

Phosphate deprivation and acute respiratory alkalosis both stimulate phosphate conservation by the kidney. To evaluate the response of the superficial proximal tubule to increases in the filtered load of phosphate (Pi), micropuncture studies were performed in these two models of Pi conservation, rats fed a low-phosphate diet (0.07% Pi), and rats with acute respiratory alkalosis (RA). All animals were acutely thyroparathyroidectomized. After basal collections, the animals were infused with Pi at a rate of 4 microM/min and then the samples recollected 30 min after the initiation of the Pi infusion. Infusion of phosphate increased the filtered load of phosphate (FLPi) of single nephrons from 112 +/- 13 to 266 +/- 44 pmol/min in phosphate-derived rats and from 123 +/- 21 to 217 +/- 44 pmol/min in respiratory alkalotic rats. However, absolute reabsorption of phosphate (ARPi) increased only in phosphate deprivation (94 +/- 16 to 126 +/- 25 pmol/min). These results indicate that the superficial proximal convoluted tubule responds to phosphate infusion by increasing reabsorption in the phosphate-deprived model, but not in the respiratory alkalotic model, of phosphate conservation.

Absorption↗
PubMed1985

Percutaneous transluminal angioplasty for renovascular hypertension.

Five children with renovascular hypertension were treated with percutaneous transluminal angioplasty, and followed for 12 to 32 months. Blood pressure fell to normal in four patients and improved in one. Angiographic and endocrinological improvements were associated with a fall in blood pressure and no complications were observed. Angioplasty is considered a safe, effective treatment for children with renovascular hypertension.

Adolescent↗
PubMedDate not supplied

Behçet's disease presenting with a right atrial vegetation.

Behçet's disease (BD) is difficult to diagnose in children because patients often do not have characteristic symptoms and pediatricians have a low awareness of BD. We report on the case of BD in a 12-year-old boy that presented as endocarditis. Prednisolone, started after infective endocarditis had been ruled out, had a dramatic effect. Cardiac involvement in BD and the differential diagnosis of endocarditis are discussed.

Behcet Syndrome↗