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Biomedical subjects

G Yasuda

Publications and source records attributed to G Yasuda.

53 records · Page 3Linked to original sources

Effects of intranasal administration of atrial natriuretic hormone on spontaneously hypertensive rats.

The effects of the intranasal administration of synthetic alpha-human atrial natriuretic polypeptide (alpha-hANP) were investigated in 14 anesthetized spontaneously hypertensive rats (SHR; Okamoto-Aoki strain). They were given intranasally synthetic alpha-hANP in distilled water at doses of 10 micrograms/kg, 50 micrograms/kg and 100 micrograms/kg. Intranasal application of 200 microliter of distilled water as a control was also performed in 3 anesthetized SHR. Sixteen anesthetized SHR were examined for the effects of intravenous administration of alpha-hANP at doses of 4 micrograms/kg, 10 micrograms/kg, 20 micrograms/kg and 40 micrograms/kg. Urinary volume and the urinary excretion of sodium increased 2- to 3-fold during the 50 minutes following intranasal administration of a single dose of 50 micrograms/kg or 100 micrograms/kg, although neither the urinary volume nor the urinary excretion of sodium increased after intranasal administration of 10 micrograms/kg of alpha-hANP or 200 microliter of distilled water. There were no significant changes in arterial pressure or heart rate after the intranasal administration of synthetic alpha-hANP or distilled water. In contrast, arterial pressure was decreased and urinary volume and urinary excretion of sodium were increased, in a dose dependent manner, within 5 minutes after intravenous bolus-injection of alpha-hANP and returned to their baseline levels within 20 minutes. These results indicate that intranasal administration of synthetic alpha-hANP exerts its diuretic effect without concomitant changes in arterial pressure or heart rate in SHR.

Administration, Intranasal↗

Renal haemodynamics and comparative effects of captopril in patients with benign- or malignant-essential hypertension, or with chronic renal failure.

Effects of captopril on arterial pressure (AP) and renal function were investigated in patients with non-malignant "benign" or malignant phase essential hypertension (EH group), or with chronic renal failure (CRF group). After captopril administration, AP and renal vascular resistance (RVR) decreased significantly, and renal blood flow (RBF) and plasma renin activity (PRA) increased in both groups. Glomerular filtration rate (GFR) increased in the EH group, but was unchanged in CRF. Filtration fraction decreased in the malignant hypertension and CRF groups. Significant correlations were found between baseline PRA and baseline RVR, and the captopril-induced decrease in mean AP, decrease in RVR, increase in RBF, and increase in GFR in the EH group, while these associations were not observed in CRF. These results indicate that the high AP, RVR, suppressed RBF and GFR in the EH group were closely related to activity of the renin-angiotensin system, but not so the low RBF and GFR in CRF. Small doses of captopril may improve impaired renal function in EH, and may not cause deterioration in the CRF group.

Captopril↗

Pharmacokinetics and acute effect on the renin-angiotensin system of delapril in patients with chronic renal failure.

The acute effect on the renin-angiotensin system and the pharmacokinetic properties of delapril, a new angiotensin converting enzyme inhibitor and its active diacid metabolites (delapril diacid and 5-hydroxy delapril diacid) arising from delapril in vivo were investigated in 4 hypertensive patients with chronic renal failure (CRF: 4 males, average age 49.5 (37-64) years, mean Ccr 22.2 ml/min/1.73 m2) and 9 patients with essential hypertension (EH: 6 males, 3 females, average age 42.8 (28-61) years, mean Ccr 79.3 ml/min/1.73 m2). In CRF, following a single dose of delapril hydrochloride (30 mg), the biological half lives (t1/2) of delapril diacid and 5-OH-delapril diacid were 4.69, 12.88 hours, the maximum serum concentration (Cmax) and the area under the plasma concentration-time curve ([AUC]24(0)) of delapril and its diacid metabolites were 414, 797 and 435 ng/ml, and 658, 6400 and 5068 ng X h/ml, respectively. In EH, the t1/2 of delapril diacid and 5-OH-delapril diacid were 1.21, 1.40 hours and the Cmax and [AUC]24(0) of delapril and its diacid metabolites were 489, 635 and 229 ng/ml, and 572, 1859 and 948 ng X h/ml, respectively. The [AUC]24(0) in CRF were significantly increased as compared with those in EH. The cumulative urinary excretions were significantly lower in CRF than in EH. The serum angiotensin converting enzyme (ACE) was markedly inhibited in both groups up to 24 hours. The plasma concentration of angiotensin II decreased in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗

Preoperative lateralisation of aldosteronomas by aldosterone/cortisol ratios in adrenal venous plasma.

Data from adrenal scintigraphy with 6 beta-[131I]-iodomethyl-19-norcholesterol (AS), computed tomography (CT), adrenal venography and adrenal venous sampling were compared for their accuracy in locating small aldosteronomas in 17 patients. Final confirmation of location was by surgery. Seventeen out of 18 adrenals whose aldosterone/cortisol (A/C) ratio was 5.0 x 10(-3) or higher were found to have aldosteronomas (94.4%). All 14 adrenals whose A/C ratios were less than 5.0 x 10(-3) contained no aldosteronomas (100%). AS successfully lateralised nine out of 17 aldosteronomas (52.9%), CT 3 out of 5 (60.0%), adrenal venography 12 out of 17 (70.6%), adrenal venous aldosterone concentration 12 out of 15 (80.0%). The most frequent problem with adrenal venous sampling was the varying degrees of mixture with non-adrenal venous blood, mainly from renal vein and inferior vena cava blood. The A/C ratio of adrenal venous plasma proved to be the most useful diagnostic tool, using cortisol concentration as an indicator of any non-adrenal venous mixture.

Adenoma↗

Existence of renal alpha 1- and alpha 2-adrenoceptors in the human kidney: radioligand binding study in membranes from the human renal cortex and medulla.

We investigated alpha 1- and alpha 2-adrenoceptors by radioligand binding studies in plasma membranes from the human renal cortex and medulla using a new alpha 1-adrenoceptor antagonist, 3H-bunazosin, and an alpha 2-adrenoceptor antagonist, 3H-rauwolscine. Human kidneys were obtained post-mortem (n = 4) or at surgery for carcinoma of the kidney (n = 10). The specific binding of both radioligands was rapid, saturable, reversible and specific. Scatchard analysis of 3H-bunazosin binding showed that the renal cortex had a KD of 4.6 nmol/l and a Bmax of 34.7 fmol/mg of protein, and the medulla a KD of 2.4 nmol/l and a Bmax of 23.2 fmol/mg. The specific binding of 3H-rauwolscine had a KD of 5.6 nmol/l and Bmax of 22.4 fmol/mg of protein for the cortex and values of 5.1 and 42.0, respectively, for the medulla. Competitive inhibition studies suggested that the binding of both radioligands was to sites with alpha 1 and alpha 2 specificity, respectively. The present studies demonstrate that human renal plasma membranes from both the cortex and medulla contain binding sites with both alpha 1- and alpha 2-adrenoceptors.

Humans↗

Serum concentration and effects of a single dose of enalapril maleate in patients with essential hypertension.

The antihypertensive effect of a non-sulfhydryl, long acting ACE (angiotensin converting enzyme) inhibitor, MK-421, was evaluated by administering a single dose of 10 mg to 13 patients with mild to moderate essential hypertension. The pharmacokinetic profile of MK-421 and its potent active metabolite, MK-422, was also assessed, together with the effect on the various components of the renin-angiotensin system. A single dose of MK-421 produced a significant fall in MBP from 2 to 24 hours post-drug. As could be expected, plasma ACE activity was suppressed up to 24 hours after MK-421. The half-life of MK-422, Cmax and [AUC]24(0) of MK-421 and MK-422 were measured. No significant change in plasma bradykinin or urinary excretion rate of kallikrein was observed, whereas a slight increase was observed in the urinary excretion rate of kinins after MK-421 in 8 patients. Significant correlations were observed between pretreatment PRA levels and the maximum fall in MBP.

Adult↗

Bilateral pheochromocytoma associated with papillary adenocarcinoma of the thyroid gland; report of an unusual case.

A 31-year old woman was admitted to our clinic complaining of high blood pressure, dizziness, constipation, mental irritability and weight loss. The physical examination revealed goiter in her neck. The plasma levels of norepinephrine and epinephrine were 3.45 and 0.76 ng/ml, respectively. Urinary excretion of norepinephrine was 1 mg and epinephrine was 32.2 micrograms/24-hours. The examination by radiography and radioactive isotope revealed a tumor in the left adrenal region and another in the left lower lobe of the thyroid. After the operations, pheochromocytoma and papillary adenocarcinoma of the thyroid gland were recognized pathologically. However, 17 months later, the recurrence of pheochromocytoma in the contralateral adrenal region was discovered and removed. Although the co-existence of bilateral pheochromocytoma and papillary adenocarcinoma of the thyroid gland is not one of multiple endocrine neoplasia, to the best of our knowledge, only 7 such cases have been reported in the published literature.

Adenocarcinoma, Papillary↗

Pharmacological properties of presynaptic beta-adrenoceptors in guinea-pig pulmonary arteries.

Pharmacological properties of the facilitatory presynaptic beta-adrenoceptor mechanism were studied in superfused spiral preparations of guinea-pig pulmonary arteries preloaded with 3H-norepinephrine. (-)-Isoproterenol (0.3 microM)-induced increases in total 3H efflux per pulse evoked by transmural field stimulation (1, 5, 10 and 20 Hz, 10 V, 2 msec pulse width, 100 pulses and 30 min intervals) were neither dependent on impulse-frequencies nor selective at lower frequencies. Isoproterenol increased 3H efflux at 5 Hz in a concentration-dependent manner (1 nM to 1 microM): pD2 was 7.7. Salbutamol increased 3H efflux in a similar manner to isoproterenol: pD2 was 7.4. Prenalterol at 3 microM only slightly increased 3H efflux. Tazolol (10 nM to 3 microM) produced no increases. Atenolol (3 microM) and practolol (3 microM) did not antagonize isoproterenol (0.3 microM)-induced increases in 3H efflux. Butoxamine (3 microM) and H 35/25 (3 microM) did antagonize this parameter. (-)-Epinephrine (1 nM to 0.1 microM) decreased 3H efflux at 5 Hz and concentration-dependently increased this parameter in the presence of 10 microM phentolamine. (-)-Norepinephrine (10 nM to 1 microM) concentration-dependently inhibited evoked 3H efflux and did not increase the parameter in the presence of 10 microM phentolamine, 10 microM cocaine and 10 microM normetanephrine. Thus, there exist presynaptic beta 2-subtype receptors on noradrenergic nerve endings innervating guinea-pig pulmonary arteries.

Adrenergic beta-Agonists↗

Characteristic localization of alpha 1- and alpha 2-adrenoceptors in the human kidney.

1. The localization of alpha-adrenoceptors in the plasma membranes of human kidney were investigated by radioligand binding, using an alpha 1-antagonist, [3H]-bunazosin, and an alpha 2-antagonist, [3H]-rauwolscine. 2. Both the maximum binding (Bmax) and dissociation constant (Kd) of [3H]-bunazosin were greater in the cortex than in the medulla. The Bmax of [3H]-rauwolscine in the medulla was greater than in the cortex. 3. Thus, alpha 1-adrenoceptors appeared to be localized predominantly in the cortex, while the alpha 2-adrenoceptors were mainly present in the medulla of the human kidney.

Adrenergic alpha-Antagonists↗