[Symposium--drug metabolism and drug action. 6. Duration of sleep induced by hexobarbital following thyroidectomy hexobarbital metabolism].
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Animals↗
Biomedical subjects
H Takase
Publications and source records attributed to H Takase.
[Extraperiosteal paraffin insertion for the treatment of pulmonary tuberculosis].
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Adult↗
Age-related changes of bile acid metabolism in rats.
Cholesterol and bile acid leves were examined in young (8 weeks), middle-aged (12 months) and old (24 months) germ-free male rats, and young (8 weeks) and middle-aged (12 months) conventional male rats. The plasma cholesterol levels were higher in the aged rats, being more marked in the conventional rats. The liver cholesterol levels also increased with age and the increases were almost identical for both groups. No age-related changes were found in the biliary bile acid secretion, the pool size and distribution of bile acids in the bile, small intestine and large intestine, nor in the turnover frequency of bile acids, but the pool size in the young and middle-aged germ-free rats was much larger than that in the conventional rats. The turnover frequency was less in the germ-free rats. The bile acid synthesis presumed from the fecal bile acid excretion decreased in the aged germ-free rats but not in the conventional rats. A most remarkable age-related change was found in the bile acid composition; cholic acid increased and beta-muricholic acid derived from chenodeoxycholic acid in the rat decreased by aging, resulting in an increase of the CA/CDCA ratio (bile acids belonging to the cholic acid group/bile acids to the chenodeoxycholic acid group) in the bile, feces and pool. These results suggest that cholic acid synthesis increases while chenodeoxycholic acid synthesis is impaired by aging in rats.
Journal Article↗
Bile acid synthesis in young and old rats.
Bile acid synthesis from orally administered (14)C-cholesterol or from (14)C-mevalonic acid administered intravenously were examined in male and female 2-, 12- and 24-month-old rats. About 5-9% of the '4C-cholesterol administered was recovered as bile acids from the small intestine 3 days after administration. The value in the case of (14)C-mevalonic acid was about 1/10 that of (14)C-cholesterol. Major bile acids were cholic acid and beta-muricholic acid, and the formation ratio of cholic acid increased in aged rats, although no further difference was found between 12- and 24-month-old animals of either sex. Male rats formed more beta-muricholic acid than females at all ages examined. In addition, no significant difference was found in the bile acid composition between both precursors, (14)C-cholesterol and (14)C-mevalonic acid.
Journal Article↗
Chronic blockade of nitric oxide-synthase and endothelin receptors during pregnancy in the rat: effect on pregnancy outcome.
OBJECTIVES: To investigate the effects of endothelin-1 (ET-1) receptor antagonism and/or chronic blockade of nitric oxide (NO) production on pregnancy outcome in the rat. METHODS: Pregnant or nonpregnant Wistar rats were either treated orally for up to 18 days with the NO-synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME), the ETA-/ETB-receptor antagonist bosentan (Roche Basel, Switzerland) or both, or received no treatment (controls). Blood pressure, body weight, and drug intake were measured at regular intervals. Pregnancy outcome and proteinurea were also determined. Analysis of variance and paired Student t test were used for statistical analysis. RESULTS: Chronic L-NAME treatment increased systolic blood pressure by 69 and 64 mmHg in pregnant and virgin rats respectively (P < .05). Bosentan-blunted, L-NAME-induced hypertension at the beginning (P < .05), but not at the end of the treatment period in all rats examined. N omega-nitro-L-arginine methyl ester-treatment in pregnancy reduced the number of living fetuses at term (P < .05) and caused proteinurea (P < .05). Bosentan tended to reverse the effects of L-NAME on fetus number and proteinurea, but both effects failed to reach statistical significance. CONCLUSIONS: The effects of chronic, NO-synthase-blockade on blood pressure in gravid rats can be reversed only temporarily by ETA-/ETB-antagonism, suggesting an involvement of endothelin-1 in the early phase of the L-NAME-induced, preeclampsia-like syndrome during pregnancy, although at later stages other mechanisms may come into play.
Animals↗
Chronic blockade of nitric oxide synthase and endothelin receptors during pregnancy in the rat: effect on reactivity of the uterine artery in vitro.
OBJECTIVE: To investigate the effects of chronic blockade of nitric oxide (NO) production and endothelin (ET-1) receptor antagonism on endothelial and vascular smooth muscle function of the uterine artery in vitro obtained from nonpregnant and pregnant rats. METHODS: Pregnant or nonpregnant Wistar rats were either treated orally for up to 18 days with the NO synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME), the ETA-/ET beta-receptor antagonist bosentan, or both, or they received no treatment (controls). Absolute contractile force as well as endothelium-dependent and -independent vascular reactivity of uterine arteries were determined in vitro. Isometric tension was recorded. ANOVA and the Mann-Whitney U test were used for statistical analysis. RESULTS: Pregnancy increased absolute tension (mN/mm) elicited in uterine arteries by ET-1 (P < .01), serotonin (P < .05), norepinephrine (P < .02), and KCl (P < .0001). Chronic treatment with L-NAME or L-NAME plus bosentan, but not with bosentan alone, reduced contractions to KCl in pregnant and nonpregnant rats (P < .005-.0001), while pregnancy-induced enhancement in tension development remained unchanged in all groups (P < .005). After exposure of uterine arteries to L-NAME in vitro, vascular sensitivity to ET-1 was augmented in uterine arteries of pregnant but not of nonpregnant animals (P < .05). L-NAME-pretreatment did not influence the pregnancy-induced increase of vascular sensitivity to acetylcholine but reduced maximal relaxation in nonpregnant animals (P < .05). In addition, pregnancy diminished sensitivity of uterine arteries to sodium nitroprusside (P < .002), which was abolished by chronically administered L-NAME. Bosentan had no influence on vasodilation in vitro. CONCLUSION: Neither endothelin-1 nor nitric oxide seem to contribute to the augmented tension to depolarization and receptor-operated stimulation of vascular smooth muscle cells in rat uterine arteries during pregnancy. In addition, pregnancy is associated with increased NO production in uterine arteries, as evidenced by augmented endothelium-dependent relaxations, increased NO release by endothelin-1, and decreased sensitivity to sodium nitroprusside.
Acetylcholine↗
Aging, serum estradiol levels, and pregnancy differentially affect vascular reactivity of the rat uterine artery.
OBJECTIVES: To investigate the effects of aging, ovarian ablation, and pregnancy on vascular reactivity of the rat uterine artery. METHODS: Segments of uterine artery from 3-month-old pregnant and nonpregnant Wistar rats and from aged and ovariectomized animals, both 9 months of age, were exposed in vitro to vasoactive mediators. Absolute contractile force as well as endothelium-dependent and -independent vascular reactivity were determined. Isometric tension was recorded using a modified Mulvany myograph system. Results were compared with analysis of variance and Bonferroni-Dunn post hoc analysis and correlated with serum estradiol levels. RESULTS: Aging up to 9 months decreased absolute tension of uterine arteries in vitro elicited by KCl (P < .0001), while not affecting receptor-operated responses to norepinephrine, endothelin-1, and angiotensin II. After ovarian ablation maximal contraction to norepinephrine was selectively reduced in the aged animal (P = .0053). Pregnancy increased absolute tension to KCl (P < .0001), norepinephrine (P < .008), and endothelin-1 (P = .0003), whereas relative contractile force (percentage of KCl) induced by norepinephrine and endothelin-1 remained unchanged and that induced by angiotension II decreased (P = .0001) in pregnant animals. In addition, pregnancy increased sensitivity to the endothelium-dependent vasodilator acetylcholine (P = .0022) but decreased that to the endothelium-independent vasodilator sodium nitroprusside (P = .0062). Endothelium-dependent relaxation correlated with serum estrogen levels remained unchanged in 9-month-old Wistar rats, which physiologically exhibited high serum estrogen concentrations but was impaired with regard to both maximum relaxation (P < .0001) and sensitivity in aged rats (P = .0007) after ovariectomy. CONCLUSIONS: Vascular contractility is impaired in the uterine artery of the aged rat as evidenced by reduced responses to KCl, whereas responses to receptor-operated agonists remain unchanged. Functional ovaries are essential to preserve endothelium-dependent relaxation in aging animals. During pregnancy, contractile machinery and endothelium-dependent relaxation are enhanced. In contrast, contractions to angiotensin II and endothelium-independent relaxation to sodium nitroprusside are reduced in late pregnancy. These changes in reactivity of the uterine artery may be important for the regulation of blood flow in the uterus according to physiologic needs.
Acetylcholine↗