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Biomedical subjects

H Iwao

Publications and source records attributed to H Iwao.

At least 109 records · Page 6Linked to original sources
PubMed1993

Effects of EXP3174, a non-peptide angiotensin II receptor antagonist, on renal hemodynamics and renal function in dogs.

We examined the effects of intrarenal infusion of EXP3174, a non-peptide angiotensin II receptor antagonist, in order to evaluate the physiological role of endogenous angiotensin II in regulating renal hemodynamics and urine formation and to assess the possibility of a tubular site(s) of action of endogenous angiotensin II in anesthetized dogs. Intrarenal infusion of EXP3174 at 15 micrograms/kg per min caused increases in renal blood flow (RBF), glomerular filtration rate (GFR), urine, flow and urinary electrolyte excretion. The lower dose of EXP3174 (0.5 micrograms/kg per min) did not change mean arterial pressure, RBF and GFR, but did increase urine flow. The fractional excretion of sodium, the fractional proximal excretion of sodium and the fractional distal excretion of sodium increased with lower doses of EXP3174 infusion. EXP3174 did not affect the linear relationship between the free water reabsorption rate and osmolar clearance. These data suggest that endogenous angiotensin II plays a significant role in regulating renal hemodynamics and urine formation and endogenous angiotensin II stimulates sodium reabsorption in the proximal and the distal portions of the tubules, with the exception of the medullary portion of the ascending limb of Henle.

Angiotensin II↗
PubMed1993

Effect of the platelet-activating factor antagonist, TCV-309, and the cyclo-oxygenase inhibitor, ibuprofen, on the haemodynamic changes in canine experimental endotoxic shock.

1. The present study was conducted in order to examine the effects of the platelet-activating factor (PAF) antagonist, TCV-309, and the cyclo-oxygenase inhibitor, ibuprofen, on the acute haemodynamic responses to endotoxin in anaesthetized dogs. 2. Endotoxin (2 mg kg-1, i.v.) induced a severe hypotension by decreasing both total peripheral resistance (TPR) and cardiac output. Endotoxin also decreased central venous pressure and increased effective vascular compliance (EVC), indicating a blood pooling in the capacitance vessels. 3. The endotoxin-induced hypotension but not the fall in cardiac output, was markedly attenuated by ibuprofen. Ibuprofen abolished the decrease in TPR and even caused a systemic vasoconstriction. Ibuprofen abolished the increase in EVC. 4. The hypotension caused by endotoxin was attenuated by TCV-309 to a lesser extent than ibuprofen. However, the reduction in cardiac output produced by endotoxin was markedly attenuated by the PAF antagonist. TCV-309 also abolished the increase in EVC. In contrast to ibuprofen, TCV-309 did not affect the decrease in TPR caused by endotoxin. 5. Combined treatment with ibuprofen and TCV-309 markedly attenuated the endotoxin-induced hypotension, but not the fall in cardiac output. Nevertheless, when compared with animals treated with ibuprofen alone, treatment with ibuprofen and TCV-309 partly attenuated the endotoxin-induced reduction in cardiac output and systemic vasoconstriction. 6. These data indicate that dilatation of both resistance vessels and capacitance vessels contributes to the endotoxin-induced hypotension. It is suggested that (i) both prostanoids and PAF are involved in dilatation of capacitance vessels, (ii) prostanoids, but not PAF cause dilatation of resistance vessels and(iii) PAF may partly contribute to prostanoid-independent reduction in cardiac output in acute canine experimental endotoxin shock.

Animals↗
PubMed1993

Effect of NG-nitro-L-arginine on effective vascular stiffness in dogs.

It has been reported that there is a continuous release of nitric oxide (NO) that contributes to the regulation of vascular tone in the arterial system. In contrast, the role of NO on vascular tone in the venous system is controversial. We examined the effect of NG-nitro-L-arginine (LNNA), an NO synthase inhibitor, on venous tone in dogs. Venous tone was evaluated by effective vascular stiffness (EVS), which was calculated from the changes in central venous pressure recorded simultaneously with changes in blood volume. LNNA (10 mg/kg, i.v.) increased EVS from 0.21 +/- 0.04 to 0.30 +/- 0.03 mmHg.kg/ml as well as increasing the systemic vascular resistance. NG-Nitro-D-arginine had no effect on EVS. The LNNA-induced increase in EVS was partly reversed by L-arginine, but not by D-arginine, indicating that the increase in EVS was attributable to a blockade of NO synthesis. Since the present study was conducted under ganglion blockade, nitroxidergic nerve terminals do not seem to be the source of NO in this case. These findings suggest that NO (endothelium-derived relaxing factor) is constantly released in the venous system and contributes to the regulation of total systemic venous tone.

Animals↗
PubMed1992

Effects of semotiadil fumarate (SD-3211) on renal hemodynamics and function in dogs.

Studies were carried out to define the effect of semotiadil on renal hemodynamics, renal function and renin release in pentobarbital-anesthetized dogs. Intrarenal arterial infusion of semotiadil resulted in a significant increase in renal blood flow (RBF), glomerular filtration rate (GFR), urine flow, urinary excretion of electrolytes and renin release. Semotiadil did not affect the linear relationship between osmolar clearance and the free water reabsorption rate, and increased the urinary excretion of sodium and calcium to the same extent. These results suggest that the main tubular site of action of semotiadil is the proximal tubule. Intrarenal infusion of a potent non-peptide angiotensin II antagonist, DuP753 (15 micrograms/kg per min), resulted in an increase in RBF, GFR, urine flow and UNaV. In spite of the blockade of the intrarenal renin angiotensin system(RAS) with DuP753, semotiadil caused almost the same effects as it did in the absence of DuP753. These results suggest that the renal effects of semotiadil are independent of the intrarenal RAS.

Analysis of Variance↗
PubMed1992

Effect of L-NG-nitro-arginine, inhibitor of nitric oxide synthesis, on autoregulation of renal blood flow in dogs.

The present experiments were designed to evaluate the importance of nitric oxide in the regulation of renal hemodynamics and the autoregulation of renal blood flow (RBF) in anesthetized dogs. RBF was measured by an electromagnetic flowmeter, and renal arterial pressure (RAP) was varied by an adjustable aortic clamp. The RAP-RBF relations were examined during the intrarenal infusion of saline or agents. The intrarenal infusion of L-NG-nitro-arginine (L-NNA, 40 micrograms/kg.min) at normal RAP decreased RBF and urine flow (UF), while the infusion of L-arginine.HCI (1 mg/kg.min) increased RBF and UF. Both agents did not affect the glomerular filtration rate and mean arterial pressure. The autoregulation of RBF was impaired during the L-NNA infusion. The L-arginine infusion did not affect autoregulatory efficiency. When L-NNA (40 micrograms/kg.min) and L-arginine were infused simultaneously into the renal artery, the autoregulation of RBF was maintained. However, a higher dose of L-NNA (200 micrograms/kg.min) impaired the autoregulation of RBF. These results suggest that the basal production and/or the release of nitric oxide contributes to the regulation of renal hemodynamics and urine formation. During the reduction of RAP, nitric oxide may play an important role in the autoregulation of RBF.

Animals↗
PubMed1992

Regional hemodynamic effects of betaxolol, a new selective beta 1-blocker, and atenolol in conscious spontaneously hypertensive rats.

Betaxolol is a new beta-blocker that has been reported to have beta 1-selectivity, and it is devoid of both membrane stabilizing action and intrinsic sympathomimetic action. The effects of betaxolol on systemic and regional hemodynamics were examined in conscious spontaneously hypertensive rats (SHR) by a microsphere method and compared with the effects of atenolol. A single oral administration of betaxolol at 1 and 10 mg/kg decreased the mean arterial pressure in a dose-dependent manner. At the same doses, atenolol also showed a similar but weak hypotensive effect. Both of these drugs at the high dose decreased cardiac output and heart rate and at the low dose, did not. Total peripheral resistance decreased by only betaxolol at the low dose. Betaxolol showed a tendency to normalize the hemodynamic abnormalities which were observed in the kidney, spleen and gastrointestinal tract of SHR, while atenolol did not. It should be noted that betaxolol increased the flow rate in the kidney, which may be explained by its direct vasodilatory action on renal blood vessels. In conclusion, betaxolol showed an antihypertensive action at the doses of 1 and 10 mg/kg, exhibited the characteristics of a beta 1-blocker and produced preferable effects on regional hemodynamics in SHR.

Animals↗
PubMed1992

Effects of the calcium antagonist manidipine on renal hemodynamics and function in dogs: comparison with nifedipine.

The renal effects of manidipine, a new dihydropyridine calcium antagonist, were compared with those of nifedipine in anesthetized dogs. Intrarenal administration of manidipine 1 and 5 micrograms/kg resulted in prolonged (120 min) increases in renal blood flow (RBF), glomerular filtration rate (GFR), urine flow (UF), and urinary excretion of electrolytes. In contrast, the renal effects of nifedipine disappeared within 5 to 10 min after administration. These results demonstrate that manidipine is a long-acting calcium antagonist. Manidipine proportionally increased RBF and GFR. As a result, filtration fraction was kept constant. The changes in afferent and efferent arteriolar resistance suggested that manidipine increases GFR via dilation of afferent arterioles with subsequent elevation of filtration pressure in the glomeruli. Manidipine also proportionally increased Tc H2O and Cosm; Tc H2O/Cosm did not change throughout the experiments. In addition, manidipine increased the fractional excretion of sodium from the distal tubule which was calculated from the lithium and sodium clearance. The mode of diuretic action of manidipine most likely involves inhibition of sodium reabsorption in the proximal and distal tubules, except the medullary portion of the ascending limb of Henle. The renal vascular site of action of manidipine might be the afferent arteriole.

Anesthesia↗
PubMed1992

[Molecular pharmacology in diuretics].

Recently, much knowledge of the molecular mechanism of diuretic actions has been accumulated. Molecular cloning of carbonic anhydrase revealed a difference in isozymes and the localization of each isozymes was also identified. Carbonic anhydrase VI, located in brush border of the proximal tubules, is inhibited by acetazolamide. Loop diuretics, furosemide, bumetanide, piretanide and ethacrynic acid, inhibit Na(+)-K(+)-Cl(-)-cotransport system in the thick ascending limb of the Henle's loop. The histochemical localization and biological characterization were investigated by using [3H]-bumetanide. Loop diuretics cotransport protein and inhibit Na+ and Cl- reabsorption. Spironolactone inhibits the binding of aldosterone and cytosol mineralocorticoid receptor in the cortical connecting tubule competitively.

Carbonic Anhydrase Inhibitors↗
PubMed1992

[Successful surgical treatment by Konno aortoventriculoplasty in 2 cases of congenital aortic valvular stenosis].

Konno's aortoventriculoplasty was performed in two children aged 6 years and 10 years old with congenital aortic valvular stenosis. One had previous aortic valvotomy at 21 days of age. Preoperative peak systolic pressure gradients between the left ventricle and the aorta were 120 and 140 mmHg, respectively. The original diameter of the aortic valve ring were 12 mm and 16 mm and one had supra-annular aortic stenosis whose diameter was 7 mm. The 19 mm and 23 mm SJM prosthetic valves were inserted in the subcoronary position. The postoperative course was uneventful. Their ECG showed sinus rhythm with complete right bundle branch block. Both two patients made good recovery regarding clinical data and symptoms.

Aorta↗
PubMed1991

Effects of cromakalim on renal hemodynamics and function in dogs: comparison with nicardipine.

The effects of cromakalin, a potassium channel opener, on renal hemodynamics and renal function were investigated in pentobarbital-anesthetized dogs. Intrarenal infusion of cromakalim at 0.5 micrograms/kg/min resulted in significant increases in renal blood flow (RBF), glomerular filtration rate (GFR), urine flow, and renin release. The urinary excretion rate of sodium increased by the same proportion as that of calcium. Free water reabsorption rate/osmolar clearance did not significantly change throughout the experiments. These data suggest that cromakalim did not inhibit sodium transport at the medullary portion of the ascending limb of Henle's loop and may have increased the delivery of sodium to Henle's loop. Intrarenal infusion of nicardipine increased RBF, GFR, urine flow, and the urinary excretion of electrolytes (Na, K, and Ca). The renal effects of cromakalim were very similar to those of nicardipine. Cromakalim was superimposed on a nicardipine infusion of a maximal effective dose. Superimposition of cromakalim to the nicardipine infusion did not cause any additional changes in renal hemodynamics and renal function. These data suggest that cromakalim and nicardipine exert their effects on renal hemodynamics and function via the same pathway.

Animals↗
PubMed1991

Sodium and potassium in red blood cells of premature infants during the first few days: risk of hyperkalaemia.

Erythrocyte sodium and potassium were studied in 64 newborn infants including 21 very low birthweight infants (birthweight less than 1500 g) during the first three days after birth. Erythrocyte sodium showed a positive correlation with gestational age (r = 0.63, p less than 0.01) and birthweight (r = 0.66, p less than 0.01). Erythrocyte potassium was negatively correlated with birthweight (r = -0.33, p less than 0.05). The Na/K ratio in red blood cells showed a positive correlation with gestational age (r = 0.60, p less than 0.01) and birthweight (r = 0.65, p less than 0.01). In VLBW infants plasma potassium rose significantly (p less than 0.01) from 0-6 h to 12-30 h and decreased from 12-30 h to 30-60 h (p less than 0.05). Erythrocyte potassium decreased slightly from 0-6 h to 12-30 h, but not significantly. A new finding that "more immature infants have higher potassium and lower sodium concentration in RBC" may suggest a potential risk of hyperkalaemia in tiny infants.

Erythrocytes↗
PubMed1991

High-dose intravenous gammaglobulin therapy for neonatal immune haemolytic jaundice due to blood group incompatibility.

Three newborn infants who developed hyperbilirubinemia due to blood group incompatibility were treated with high-dose gammaglobulin. Hyperbilirubinemia was caused by Rhesus (Rh) incompatibility (anti-E + anti-c) in Infant 1 and ABO incompatibility (anti-B) in Infants 2 and 3. Hyperbilirubinemia was refractory to conventional phototherapy but responded well to intravenous gammaglobulin (IVGG) at a dose of 1 g/kg in all infants. No adverse effects were observed. These findings suggest that high-dose IVGG may be useful in the treatment of hyperbilirubinemia due to isoimmune haemolytic disease resistant to phototherapy.

Drug Combinations↗
PubMed1991

Effects of prolonged treatment with beta-adrenoceptor antagonist, carteolol on systemic and regional hemodynamics in stroke-prone spontaneously hypertensive rats.

The present study was designed to determine the regional hemodynamic effects of prolonged beta-adrenergic receptor inhibition in conscious stroke-prone spontaneously hypertensive rats (SHRSP) using a radioactive microsphere method. When the regional blood flow was compared between 10 and 30 weeks of age, the age-related changes in organ blood flow were observed in several organs, i.e., the reduction of flow rate in kidney, adrenal gland and intestines. The reduction of flow rate in these organs contributes strongly to the age-related rise of total peripheral resistance. Carteolol, a beta-adrenoceptor antagonist, was given at a dose of 10 mg/kg/d from 10 to 30 weeks of age. These animals gained more weight than the untreated control SHRSPs, and heart rate was reduced significantly. Blood pressure was not affected. However, the prolonged treatment with carteolol prevented the age-related reduction of the blood flow rate in the kidney, adrenal gland and intestines. Thus, our findings indicate that carteolol had appreciable and beneficial effects on the maintenance of flow rates in the above organs of SHRSP without any change in blood pressure.

Animals↗
PubMed1991

[Expression of the renin and angiotensinogen genes].

Recent advances in molecular biological techniques provide us with genetic approaches for studying the renin-angiotensin system. Renin and angiotensinogen cDNAs have been cloned in several species, and the sequences are highly conserved between the species. The 5'-flanking region of the human renin gene indicated putative regulatory sequences of glucocorticoid, estrogen, progesterone, and cAMP. The 5'-flanking region of the human angiotensinogen gene also had putative regulatory sequences of glucocorticoid, estrogen, acute phase protein, and cAMP. These structures may be related to the tissue specific expression of the renin and angiotensinogen genes. In this review, expression of rat renin and angiotensinogen genes in various tissues in the following conditions are described: a) different sodium intake in the liver, kidney, and brain; b) angiotensin II and converting enzyme inhibition in the liver, kidney and brain; c) renovascular hypertension in the kidney and liver; d) aging in the liver and kidney; e) adrenal steroids in the liver, kidney and brain; f) gonadotropin and testosterone in the testes, liver and kidney; g) triiodothyronine in the liver, kidney and brain; h) nephrectomy in the liver and brain; i) high potassium, angiotensin II, sodium intake and nephrectomy in the adrenal gland; j) transgenic animal. Our results suggest that the expression of the renin and angiotensinogen genes are regulated in a tissue-specific manner.

Aging↗
PubMed1991

Forskolin preferentially dilates the afferent arteriole in the canine kidney.

Intrarenal infusion of forskolin (0.2 microgram/kg/min) in anesthetized dogs increased renal blood flow (RBF) and glomerular filtration rate (GFR) to the same degree but did not change the mean arterial pressure or heart rate. Forskolin also increased urine flow and urinary sodium excretion. The proportional increases in RBF and GFR may result from a preferential action of forskolin to dilate the afferent arteriole.

Adenylyl Cyclases↗
PubMed1991

Effects of water deprivation and morphine administration on atrial natriuretic peptide mRNA levels in rat auricles.

We investigated the influences of two potent stimuli, water deprivation (5 days) and morphine administration (100 mg/kg), on the level of atrial natriuretic peptide (ANP) mRNA in the rat auricles. The ANP mRNA level was measured by Northern blot hybridization analysis. The plasma concentration of ANP decreased in water deprived rats, and the ANP mRNA levels in both auricles of these rats were lower than those of the control, particularly in the left auricle. Thirty minutes after the injection of morphine, the plasma concentration of ANP markedly increased, while morphine increased the right auricular ANP mRNA level 4 hr after the administration. These data suggest that these stimuli can change ANP gene expression in the auricles and that the changes are induced differentially in both auricles.

Animals↗
PubMed1990

Renal vasodilatation induced by DOI, a 5-HT2 receptor agonist, in the canine kidney.

An intrarenal infusion of (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), a selective 5-HT2 agonist, at a rate of 5 micrograms/min in anesthetized dogs resulted in an increase in renal blood flow (RBF) without any transient decrease as usually observed during the infusion of 5-HT. During the infusion, urine flow (UF) and urinary sodium excretion rates (UNaV) increased along with RBF while the mean arterial pressure and glomerular filtration rate did not change. After pretreatment with ritanserin, a selective 5-HT2 antagonist, DOI failed to increase RBF, UF and UNa V. It is concluded that DOI produces renal vasodilatation mediated via 5-HT2 receptors and has a diuretic action.

Amphetamines↗