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Biomedical subjects

E Kusano

Publications and source records attributed to E Kusano.

At least 91 records · Page 5Linked to original sources
PubMed1984

Distribution of alpha-adrenergic receptors in the rabbit nephron.

In order to determine the distribution of alpha-adrenergic receptors within a nephron, a method was used to determine the specific binding of [3H]-prazosin to isolated fragments of rabbit renal tubules. When 10(-8) moles/liter [3H]-prazosin was incubated with proximal convoluted tubules, 61.4% of total binding was accounted for specific binding. The [3H]-prazosin binding to the proximal convoluted tubule was a linear function of the tubular length and reversible. It was inhibited with 10(-4) moles/liter phenoxybenzamine by about 60%, and with 10(-4) moles/liter norepinephrine by about 25%, but not with either atenolol or isoproterenol. No specific binding of [3H]-prazosin was observed in the proximal straight tubule and in the cortical collecting tubule. These data are in good agreement with the view that alpha-1 adrenergic receptors are mainly distributed in the proximal convoluted tubules.

Animals↗
PubMed1984

Acute and chronic hypotensive effects of nifedipine and niludipine in hypertensive patients with chronic renal failure.

The present study was aimed to evaluate the acute and chronic hypotensive effects of nifedipine (Bay a 1040, Adalat) and niludipine (Bay a 7168) in hypertensive patients with chronic renal failure. 1. The decrease of blood pressure lasted for at least 3 h and maximum decrement was achieved in 60 min (26% decrement, p less than 0.05) after oral administration of nifedipine (10 mg). On the other hand, niludipine (20 mg) caused decrease of blood pressure for at least 4 h and attained maximum decrement in 90 min (13% decrement, p less than 0.05) after oral administration. 2. In chronic studies of both drugs, the maximum decrease of blood pressure (p less than 0.05) was attained after one week and lasted at least 4 weeks. There were no significant changes of pulse rate, body weight and urine volume in both nifedipine and niludipine groups. 3. Nifedipine caused great diurnal or day-to-day fluctuations of blood pressures after chronic administrations. On the other hand niludipine did not cause any significant fluctuations. Any serious complications could not be seen during these studies. In conclusion, these results provide clinical evidence that niludipine could be usefused great diurnal or day-to-day fluctuations of blood pressures after chronic administrations. On the other hand niludipine did not cause any significant fluctuations. Any serious complications could not be seen during these studies. In conclusion, these results provide clinical evidence that niludipine could be useful for treatment of hypertension associated with chronic renal failure. Results also suggest that the optimal efficacy of nifedipine and niludipine in part depends on the specific clinical situation at hand. For example, nifedipine seems to be the drug of choice in hypertensive emergencies when there is a need for rapid lowering of blood pressure.

Adolescent↗
PubMed1983

Concentrating defect in the adrenalectomized rat. Abnormal vasopressin-sensitive cyclic adenosine monophosphate metabolism in the papillary collecting duct.

Among other defects in water metabolism, adrenal insufficiency is associated with an inability to concentrate urine maximally in both man and experimental animals. Recent studies in the rabbit cortical collecting tubule have suggested indirectly that this defect may result from impaired cyclic AMP (cAMP) formation in response to antidiuretic hormone stimulation. In the present study, we examined key elements of arginine vasopressin (AVP)-dependent cAMP metabolism in the papillary collecting duct (PCD), microdissected from 8-d adrenalectomized (ADX) and sham-operated control rats. AVP-sensitive adenylate cyclase (ADC) activity in PCD did not differ between control and ADX rats. cAMP-phosphodiesterase activity (cAMP-PDIE), measured at 10(-6) M cAMP substrate concentration, was significantly higher (delta + 31.6%) in PCD of ADX rats compared with controls. Incubation of intact PCD from ADX rats with AVP resulted in an accumulation of cAMP (delta - 48.5%) significantly lower than observed in control PCD. Chronic administration of dexamethasone reduced cAMP-PDIE activity in PCD of ADX rats to levels close to or below those observed in control rat PCD, and also resulted in a restoration of AVP-stimulated cAMP accumulation to levels approaching control values. Results indicate that the impaired maximal urinary concentrating ability associated with adrenal insufficiency may be due, at least in part, to a reduced accumulation of cAMP in response to AVP in the PCD. This decreased cAMP accumulation results from increased cAMP-PDIE activity in the PCD of ADX rats and can be corrected by administration of glucocorticoid.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1983

Chlorpropamide action on renal concentrating mechanism in rats with hypothalamic diabetes insipidus.

To determine vasopressin (VP)-potentiating effect of chlorpropamide (CPMD), we studied the effect of CPMD in vivo and in vitro in kidneys and in specific tubule segments of rats with hypothalamic diabetes insipidus, homozygotes of the Brattleboro strain (DI rats). Rats on ad lib. water intake were treated with CPMD (20 mg/100 g body wt s.c. daily) for 7 d. While on ad lib. water intake, the urine flow, urine osmolality, urinary excretion of Na +, K +, creatinine, or total solute excretion did not change. However, corticopapillary gradient of solutes was significantly increased in CPMD-treated rats. Higher tissue osmolality was due to significantly increased concentration of Na +, and to a lesser degree urea, in the medulla and papilla of CPMD-treated rats. Consequently, the osmotic gradient between urine and papillary tissue of CPMD-treated rats (delta = 385 +/- 47 mosM) was significantly (P less than 0.001) higher compared with controls (delta = 150 +/- 26 mosM). Minimum urine osmolality after water loading was higher in CPMD-treated DI rats than in controls. Oxidation of [14C]lactate to 14CO2 coupled to NaCl cotransport was measured in thick medullary ascending limb of Henle's loop (MAL) microdissected from control and CPMD-treated rats. The rate of 14CO2 production was higher (delta + 113% +/- 20; P less than 0.01) in CPMD-treated MAL compared with controls, but 14CO2 production in the presence of 10(-3) M furosemide did not differ between MAL from control and from CPMD-treated rats. These observations suggest that CPMD treatment enhances NaCl transport in MAL. Cyclic AMP metabolism was analyzed in microdissected MAL and in medullary collecting tubule (MCT). MCT from control and from CPMD-treated rats did not differ in the basal or VP-stimulated accumulated of cAMP. The increase in cAMP content elicited by 10(-6) M VP in MAL from CPMD-treated rats (delta + 12.0 +/- 1.8 fmol cAMP/mm) was significantly (P less than 0.02) higher compared with MAL from control rats (delta + 5.1 +/- 1.0 fmol cAMP/mm). Preincubation of MAL dissected from Sprague-Dawley rats with 10(-4) M CPMD in vitro increased cAMP accumulation in the presence of VP, but no such enhancement was found in preincubated MCT. Adenylate cyclase activity, basal or stimulated by VP, 5'guanylimidodiphosphate, or by NaF, assayed in isotonic medium did not differ between MAL or MCT from control rats and MAL or MCT from CPMD-treated rats. When assayed in hypertonic medium (800 mosM), the adenylate cyclase activity in the presence of 10(-6) M VP was significantly higher in MAL of CPMD-treated rats. MAL and MCT from control and CPMD-treated rats did not differ in the activities of cAMP phosphodiesterase. The rate of [(14)C]prostaglandin E2 by medullary and papillary microsomes was not different between the control and CPMD-treated rats; likewise, there was no difference in accumulation of immunoreactive prostaglandin E2 in the medium of in vitro incubated medullary or papillary slices prepared from control and CPMD-treated rats. Based on the findings recounted above, we propose a hypothesis that CPMD administration enhances the antidiuretic effect of VP, primarily by increasing medullary and papillary tonicity dye to increased NaCl reabsorption in MAL. There is no evidence that CPMD sensitizes collecting tubules to the action of VP, at least at the camp-generation step. Therefore, increased antidiuretic response to VP in the kidneys of CPMD-treated DI rats is due to enhanced osmotic driving force for water reabsorption (lumen-to-interstitium osmotic gradient) in collecting tubules, rather than due to increased VP-dependent water permeability of tubular epithelium.

Animals↗
PubMed1982

Effects of arginine vasopressin on the thin ascending limb of Henle's loop of hamsters.

Arginine vasopressin (AVP) has been shown to stimulate active Cl transport across the medullary thick ascending limb of Henle's loop (MAL) in association with an increase in adenylate cyclase activity. To determine whether the failure to demonstrate active Cl transport across the thin ascending limb of Henle's loop (TAL) in previous in vitro perfusion studies was due to the absence of AVP in the preparation, we examined the effect of AVP on adenylate cyclase activity and Cl transport in the hamsters TAL. AVP (1 mU/ml) increased adenylate cyclase activity in the hamster TAL (20.7 +/- 5.2 control vs. 46.2 +/- 10.1 fmol . mm-1 . 30 min-1, n = 6, P less than 0.05) but not in the descending limb (27.8 +/- 7.0 control vs. 20.4 +/- 2.7, n = 4, P less than 0.05). When both MAL and TAL were perfused, a lumen-positive transepithelial voltage (Vt) was observed. The Vt was increased by adding 1 or 10 mU/ml AVP to the bath. When only the TAL was perfused, the Vt was not different from zero. Similar results were obtained in mouse renal tubules. In other experiments, AVP did not affect the diffusion potential generated when a transepithelial NaCl gradient was present. AVP or dibutyryl cAMP caused little or no change in efflux of radioactive chloride across the hamster TAL. These findings suggest that electrogenic chloride transport is not demonstrable in the TAL even in the presence of AVP. The physiologic role of AVP-sensitive adenylate cyclase in the TAL remains to be established.

Adenylyl Cyclases↗
PubMed1982

Hypotensive effect of nifedipine in hypertensive patients with chronic renal failure.

The hypotensive effect of 4-(2'-nitrophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxydimethylester (nifedipine, Adalat) was studied in 15 hypertensive patients with chronic renal failure. The decrease of blood pressure lasted for approximately 3 h and maximum decrement was achieved in 1 h after oral administration of nifedipine (10 mg). Hypotensive action of the drug was associated with a constant decrease in total peripheral resistance and an increase in cardiac output, plasma renin activity (PRA), and plasma norepinephrine (noradrenaline). Initial PRA was apparently the major determinant of the rise in PRA since a close correlation was present between the initial value and the increase induced by nifedipine (r = 0.93, p less than 0.05). Marked reduction of blood pressure without noticeable side effects was observed in two cases who had not responded to previous antihypertensive treatment. These data suggest that nifedipine exerts its hypotensive action through peripheral vasodilation and may be an effective drug for treatment of hypertension during chronic renal failure.

Adolescent↗
PubMedDate not supplied

Effect of plasmapheresis as initial monotherapy in a case of anti-neutrophil cytoplasmic autoantibody positive crescentic glomerulonephritis.

The effect of plasmapheresis (PP) monotherapy was evaluated in a 77 year old man with crescentic glomerulonephritis (CrGN). Because both anti-neutrophil cytoplasmic myeloperoxidase autoantibody (MPO-ANCA) and circulating immune complex (IC) were positive, removal of these substances was expected to be beneficial. Thus, the treatment was started with PP alone. During 2 month's time, three series of PP monotherapy were performed: three sessions of plasma exchange (PEX) with fresh frozen plasma (FFP); two sessions of double filtration plasmapheresis (DFPP); followed by another two sessions of PEX. The ANCA remained suppressed for 4 weeks after the first PEX, and increased thereafter. Subsequent DFPP caused a rebound in ANCA titer, whereas the second PEX suppressed ANCA for 1 week. Although creatinine clearance (Ccr) improved from 9.3 to 15 ml/min after the first PEX, and this level was maintained, ANCA increased again after the second PEX. Therefore, the patient was treated with methylprednisolone semi-pulse therapy (500 mg/day for 3 days), followed by mild "cocktail" therapy. In 2 weeks ANCA and IC became negative, and Ccr further improved to 20 ml/min. Thus, PP, when performed alone, was shown to be partially effective, arresting the progression of renal damage in the present case. These observations also argue for the advantage of PP, especially PEX, as an adjunct therapy to immunosuppressive therapy in CrGN.

Aged↗
PubMedDate not supplied

Utility of the inferior vena cava diameter as a marker of dry weight in nonoliguric hemodialyzed patients.

We have previously reported that the maximal inferior vena cava (IVC) diameter during quiet expiration (IVCe) measured by ultrasonography correlates well with the amount of body fluid, especially the circulating blood volume(2) and proposed using the criteria of IVC diameter to determine dry weight (DW) in anuric hemodialyzed (HD) patients: standard IVCe of pre- and post-HD are 14.9 +/- 0.4 and 8.2 +/- 0.3 mm, respectively (1). However, the same post-HD IVC criterion should not be applied to nonoliguric HD patients because it could result in rapid deterioration of residual renal function due to forced dehydration. Although the biochemical DW marker plasma atrial natriuretic peptide (ANP) is useful to evaluate hypervolemia but not hypovolemia, both hyper- and hypovolemia can be detected by IVC measurement. In the present study, we investigated whether the IVC diameter serves as an optimal evaluation of DW in nonoliguric HD (NO-HD) patients, avoiding not only overhydration but also dehydration. The IVCe and plasma ANP levels were measured in 14 euvolemic patients with chronic renal failure at conservative period (CP-CRF) and 11 NO-HD patients, in whom the average daily urine volume was more than 500 ml/day. In NO-HD patients, DW was adjusted to attain the euvolemic state with normotensive blood pressure, lack of edema, and lack of temporal oliguria after HD. The ANP in CP-CRF patients was 109.3 +/- 15.3 pg/ml, and pre- and post-HD ANP levels in NO-HD patients were 145.3 +/- 23.5 and 97.5 +/- 13.5 pg/ml, respectively. IVCe in CP-CRF was 13.4 +/- 0.9 mm, and pre- and post-HD IVCe in NO-HD patients were 14.2 +/- 1.0 mm and 11.9 +/- 0.9 mm, respectively. Although the post-HD IVCe was greater (i.e., less hypovolemic) than that in anuric HD patients, and close to the IVCe in CP-CRF, pre-HD IVCe was comparable with that in anuric HD patients. In addition, the pre-HD ANP level was no higher than that in CP-CRF. Thus, in NO-HD patients, the post-IVCe of 11.9 +/- 0.9 mm would be a marker for an appropriate DW setting avoiding severe post-HD dehydration as well as excessive hypervolemia during the interdialytic period.

Adult↗