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Biomedical subjects

M Ohashi

Publications and source records attributed to M Ohashi.

At least 379 records · Page 21Linked to original sources

Alpha-human atrial natriuretic polypeptide reduces the plasma arginine vasopressin concentration in human subjects.

The synthetic alpha-human atrial natriuretic polypeptide (alpha-hANP) was infused into six normotensive, euvolaemic, healthy volunteers to examine the effect on the plasma arginine vasopressin (AVP) concentration. The intravenous administration of alpha-hANP (0.1 microgram/kg/min, 20 min) led to a remarkable reduction in mean blood pressure (-10 mmHg, P less than 0.05), and there was an increase in pulse rate (+10 bpm, P less than 0.05), in each subject. The urinary volume, sodium excretion and cyclic 3',5'-guanosine monophosphate (cyclic-GMP) excretion were increased to 3.5 (P less than 0.05), 2.5 (P less than 0.05) eight-fold (P less than 0.01), respectively, during the alpha-hANP infusion. The dose and duration of the synthetic alpha-hANP in the present study was sufficient to induce these cardiovascular and renal effects. The plasma AVP concentrations decreased from 0.39 +/- 0.09 pg/ml to the undetectable level during the alpha-hANP administration. After infusion, the plasma concentrations of the AVP promptly returned to preinfusion levels (0.46 +/- 0.14 pg/ml). However, there was no significant change in plasma AVP concentration during placebo infusion. The marked suppression in plasma AVP concentration may account for the remarkable diuresis, in addition of the direct renal effects of the synthetic alpha-hANP.

Adult↗

Adrenocortical responsiveness to graded ACTH infusions in normal young and elderly human subjects.

The responses of plasma cortisol, aldosterone, dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEA-S) to graded ACTH infusions (from 50 mU/h to 1,000 mU/h) in elderly subjects were compared with those in young subjects. There were no significant differences between young and elderly subjects in terms of the levels of plasma cortisol during ACTH infusion. The increment in median serum cortisol increase observed in elderly subjects was also equal to that found in young subjects. Plasma aldosterone concentration showed a gradual increase in response to ACTH infusion in both young and elderly individuals. There was no significant difference between the response of young and aged subjects. Significant increases in serum DHEA in response to ACTH infusion were observed in both young and aged individuals, however, the median increase of serum DHEA (delta DHEA) in the elderly subjects was markedly lower than that in the young ones. Serum DHEA-S concentrations prior to ACTH infusion were significantly lower in the elderly subjects. With graded infusions of ACTH, plasma DHEA-S concentrations in young subjects tended to increase gradually, whereas there was no significant increase in plasma DHEA-S concentrations in the elderly. These results are indicative that the responses of adrenal androgens in elderly subjects to small, graded doses of ACTH infusion are preferentially impaired; however, the responses of cortisol and aldosterone are well maintained.

Adrenal Cortex Hormones↗

Aging is without effect on the pituitary-adrenal axis in men.

The effects of ovine corticotropin releasing factor (o-CRF) on the secretions of ACTH, cortisol, dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEA-S) were studied in the healthy young and elderly male individuals. o-CRF caused significant elevations of plasma ACTH, cortisol and DHEA concentrations, in all subjects. Moreover, there were no significant differences in the time-dependent responses of plasma ACTH, cortisol and DHEA to o-CRF between the young and elderly male individuals. o-CRF showed no significant rise of plasma DHEA-S, in all subjects. We conclude that the pituitary-adrenal sensitivity to the hypothalamic CRF in the elderly does not change with aging.

Adrenocorticotropic Hormone↗

Pharmacological actions of leukotrienes C4, D4 and E4 on guinea pig isolated taenia caecum as a preparation to study leukotrienes.

The contractile effects of leukotrienes (LTs) C4, D4 and E4 were studied in guinea pigs isolated taenia caecum. LTs C4, D4 and E4 contracted taenia caecum at low concentrations in a concentration-dependent manner. The response to LTs was not influenced by a gamma-glutamyl transpeptidase inhibitor (L-serine borate), aminopeptidase inhibitor (L-cysteine) or cyclooxygenase inhibitor (flurbiprofen), suggesting that LTC4 and LTD4 were not metabolized or metabolized only slightly in the guinea pig isolated taenia caecum, and that each of the LTs showed the direct contractile action. Furthermore, FPL55712 antagonized the response to LTD4 and LTC4 competitively but not that to LTE4. These results suggested that the guinea pig isolated taenia caecum is useful preparation to study the pharmacological actions of LTs.

Animals↗

Effect of human alpha-atrial natriuretic polypeptide on adrenocortical function in man.

To determine the effects of atrial natriuretic polypeptide (ANP) on plasma levels of ACTH, cortisol, aldosterone and dehydroepiandrosterone (DHEA), synthetic human alpha-ANP (h alpha-ANP) was infused i.v. into eight normotensive, disease-free volunteers, at a dose and duration previously found to be sufficient to produce apparent cardiovascular and renal effects. The mean basal concentration of plasma ACTH determined by radioimmunoassay was 18.2 +/- 3.1 ng/l. Plasma ACTH concentrations tended to be decreased during the infusion in all subjects. However, the change in plasma ACTH concentrations during infusion of h alpha-ANP was essentially the same as that during the infusion of saline. The mean plasma cortisol concentration was significantly suppressed from 25 to 40 min after the end of synthetic h alpha-ANP infusion. At 90 min after infusion, the mean plasma level of cortisol reverted to the pretreatment level. There was a non-significant increase in plasma renin activity following the infusion. The mean plasma aldosterone concentration was reduced by 15% (P less than 0.05) during the infusion and returned to preinfusion levels 10 min after termination of the infusion, after which the mean plasma concentration declined to the level seen during infusion. Administration of h alpha-ANP had no significant influence on plasma DHEA concentrations, but there was a tendency to decrease during the infusion. Our data suggest that synthetic h alpha-ANP inhibits adrenocortical steroidogenesis in man.

Adrenal Cortex↗

Alpha-human atrial natriuretic polypeptide-induced rise of plasma and urinary cyclic 3'5'-guanosine monophosphate concentration in human subjects.

Synthetic alpha-hANP was infused into 8 normotensive, euvolemic volunteers to examine the effects on plasma and urinary cyclic-GMP. The dose given and duration of alpha-hANP (0.1 micrograms/kg/min, 20 min) led to the significant diuresis, saliuresis and hypotensive effects in each subject. The mean plasma cyclic-GMP concentration was clearly elevated at 5 min after infusion and attained 8 fold of the mean basal concentrations by the end of infusion. The mean urinary cyclic-GMP excretion rate also showed 3.5 fold increases of the basal excretion rate with synthetic alpha-hANP administration (before loading: 0.69 +/- 0.22 p moles/g creat., after loading: 2.85 +/- 0.28 p moles/g creat.). However, there was no apparent change on plasma or urinary cyclic-AMP during the infusion. The result clearly demonstrated that synthetic alpha-hANP selectively induces the cyclic-GMP in concomitant with the marked diuretic, natriuretic and hypotensive effects in human subjects.

Adult↗

A novel type of human papilloma virus DNA from the lesion of epidermodysplasia verruciformis.

Two types of DNAs were clonally purified from the virion fraction which was obtained by the cesium chloride density gradient centrifugation of a homogenate of scrapings from benign lesions of typical epidermodysplasia verruciformis. Restriction-enzyme maps were made for these DNAs, and the DNA-DNA hybridization of these cloned DNAs with 25 different types of human papilloma virus DNAs indicated that one of the DNA clones isolated is a new type of human papilloma virus DNA, and the other is the DNA of human papilloma virus type 21 or its subtype.

Cloning, Molecular↗

A new vasodilator 3-isobutyryl-2-isopropylpyrazolo[1,5-a]pyridine (KC-404) has a dual mechanism of action on platelet aggregation.

3-Isobutyryl-2-isopropylpyrazolo [1,5-a]pyridine (KC-404) at a concentration of greater than or equal to 4.34 X 10(-5) M inhibited adenosine diphosphate-, arachidonic acid- and collagen-induced aggregation of rabbit platelets. In rabbit, KC-404 (0.5 and 2 mg/kg, i.v.) caused a decrease in weight of collagen strip extracorporeally superfused with arterial blood, because of a disaggregation of deposited platelet aggregates. This disaggregatory effect of KC-404 was markedly diminished by the pretreatment of animals with aspirin. KC-404 (greater than or equal to 4.34 X 10(-6) M) and its major metabolite diOH-KD-404 (greater than or equal to 3.78 X 10(-7) M) significantly potentiated the anti-aggregatory action of prostacyclin on rabbit platelets. KC-404 (greater than or equal to (4.34 X 10(-8) M) exerted a similar effect in rat platelets. KC-404 had no significant effect on 6-keto-PGF1 alpha and thromboxane A2 formation by rat aortic segment and rabbit platelets, respectively. KC-404 inhibited cyclic AMP phosphodiesterase (Ki = 91 microM). The present results indicate that KC-404 exhibits its anti-platelet effect via the inhibition of cyclic AMP phosphodiesterase activity in platelets and via the potentiation of anti-aggregatory activity of prostacyclin on platelets.

3',5'-Cyclic-AMP Phosphodiesterases↗

Mode of cerebral vasodilating action of KC-404 in isolated canine basilar artery.

3-Isobutyryl-2-isopropylpyrazolo[1,5-a]pyridine (KC-404) caused a potent and concentration-dependent relaxation in isolated canine basilar artery precontracted with prostaglandin (PG) F2 alpha attended by EC50 of 7.6 X 10(-8) g/ml. The relaxing action of KC-404 was little affected by the removal of vascular endothelium, whereas it was significantly diminished by pretreatment with indomethacin (10(-5) M) or acetylsalicylic acid (ASA) (10(-3) M). In PGF2 alpha-contracted canine basilar artery, KC-404-induced relaxation was markedly reversed to contraction by the subsequent addition of indomethacin (10(-5) M), ASA (10(-3) M) and phenidone (10(-4) M) by about 80%, 75% and 111%, respectively, whereas it was little affected by nordihydroguaiaretic acid (NDGA) (10(-5) M). Similar results were obtained when dipyridamole was used as a relaxant but, in contrast, papaverine-induced relaxation was little affected by indomethacin. KC-404 as well as PGI2 showed less potent or no relaxation in both PGF2 alpha-contracted rabbit aorta and KCl-contracted canine basilar artery as compared with PGF2 alpha-contracted canine basilar artery. In PGF2 alpha-contracted canine basilar artery, PGI2-induced relaxation was significantly augmented by pretreatment with KC-404 (10(-8) and 10(-7) g/ml). These results suggest that KC-404 might elicit cerebral vasorelaxation not dependent on vascular endothelium but remarkably dependent on a vasodilating cyclooxygenase metabolite, possibly PGI2.

Animals↗