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Sensitivity to antihypertensive action of hypothaiamic norepinephrine was potentiated by castration in spontaneously hypertensive rat (SHR)
enti
Kumai, T., Masubuchi, Y., Tanaka, M., Watanabe, M., Shioguchi, J.-I. and Hirai, M. Department of Pharmacologv, St. Maribnna University School of Medicine, Kawasaki, Kanagawa 213, Japan
Present study reported that role of sex hormones in mechanisms of action of naloxone as opiate antagonist to systolic blood pressure (BP) weie exauned. Castration was made a 4 weeks old (W) and experiments were carried ci9 29~36W, 58-62W and 72-78W. BP measured by tail-cuff method (KN-209). Naloxone (Nal; 10 mg/kg, SIGMA) was given i.p. and the ‘BP was measured at pm-injection, 1 to 45 min after injeciton. Catecholamine (CA) were determined with I4PI.C. Rats were divided into eight groups as I. male intact (1%Int) 2. M-Int + Nal, 3. M-castrated (M-Cast), 4. M-Cast + Nal, 5. female Int (F-Int), 6. F-lint + Nal, 7. F-Cast and 8. F-Cast + Nal. Groups 2,4,6 and 8 showed an increase of BP after treatment of Nal(2 > 1,4 > 3,6 > 5, 8 > 7) and groups 3 and 7 showed a significant decrease of BP as compared with those of Int, respectively (1 > 3.5 > 7) BP-value in group 8 reached a level comparable to that of group 6 (6 = 8). In ratio of pressor response to Nal, groups 4 and 8 were significantly higher than those of groups 2 and 6 (4 > 2, 8 > 6) meaningly that lower .androgen bearing rats have higher response to Nal. In CA analysis of male, results showed that the Cast made R trend of increase both norepinephrine (NE) and dopamine (DA) in plasma, but the epinephrine (Epi) was no-aitered. In Nal, a significant changes could not seen in plasma NE and DA both Int and Cast groups with a exception of slight increase of Epi in Int-group and that Cast was not effective on hypothalamic NE and Epi, but its DA seems a slight decreasing and that in Nal, hypothalamic NE and Epi decreased significantly in In&group, but trend of decrease was seen in Cast-group, and that hypothalamic DA was slight decreased in Cast-group but not in In&group and that in Nal, hypothalamic DA was not changed both Iut and Cast-groups, and that in hippocampus NE, Cast showed no changes and Nal treatment showed a significant increase only in Int group (2 > 1) but cot in Cast group. In female, lGiEwas not significant altered in Int by Nal, however a significant increase of NE was appeared in plasma, hippocampus, thalamus + mid-brain and hypothalamus in Cast by Nal. In Nal treatment, DA was significantly increased in plasma, hypothalamus but decreased in cerebral cortex in Int, and a tendency of increase in plasma and a significant increase in thalamus + mid-brain and hypothalamus were found in Cast. In conclusive remark as correlation between HP and hypothalamic NE in groups of castrated and noncastrated male SHR, when hypothalamic NE was increased, the BP showed lower value, in other words, while BP was increased with naloxone, hypothalamic NE decreased. However, though the pressor response by naloxone was significantly higher in Cast-group than that of In&group, the degree of decreasing was lower in the former, namely, sensitivity to antihypertensive action of hypothalamic NE was potentiated by castration. In female brain, lack of estrogen by castration provokes increase of intrinsic opiate and this accelerates the phenomenon of inhibitory action to CA release, however when Nal was administrated to Cast, actions of intrinsic opiate was blocked and, in consequence, the inhibitory action to CA was deprived and this lead to rising of CA (NE, DA)-induction.
I
P.lU.173
la-
Toorop,
G.P. and Jansen,
J.A.P.
Dept. of Pharmacology. Duphar B. V. P. 0. Box 900. 1380 DA Weesp, The Netherlandr
The centrally acting 5-HT,a agonists, 8-OH-DPAT and flesinoxan, reduce blood pressure and decrease heart rate in both anaesthetized and unanaesthetized animals via a decrease in sympathetic and an increase in vagal tone (Dreteler
Kumai, T., Masubuchi, Y., Tanaka, M., Watanabe, M., Shioguchi, J.-I. and Hirai, M. Department of Pharmacologv, St. Maribnna University School of Medicine, Kawasaki, Kanagawa 213, Japan
Present study reported that role of sex hormones in mechanisms of action of naloxone as opiate antagonist to systolic blood pressure (BP) weie exauned. Castration was made a 4 weeks old (W) and experiments were carried ci9 29~36W, 58-62W and 72-78W. BP measured by tail-cuff method (KN-209). Naloxone (Nal; 10 mg/kg, SIGMA) was given i.p. and the ‘BP was measured at pm-injection, 1 to 45 min after injeciton. Catecholamine (CA) were determined with I4PI.C. Rats were divided into eight groups as I. male intact (1%Int) 2. M-Int + Nal, 3. M-castrated (M-Cast), 4. M-Cast + Nal, 5. female Int (F-Int), 6. F-lint + Nal, 7. F-Cast and 8. F-Cast + Nal. Groups 2,4,6 and 8 showed an increase of BP after treatment of Nal(2 > 1,4 > 3,6 > 5, 8 > 7) and groups 3 and 7 showed a significant decrease of BP as compared with those of Int, respectively (1 > 3.5 > 7) BP-value in group 8 reached a level comparable to that of group 6 (6 = 8). In ratio of pressor response to Nal, groups 4 and 8 were significantly higher than those of groups 2 and 6 (4 > 2, 8 > 6) meaningly that lower .androgen bearing rats have higher response to Nal. In CA analysis of male, results showed that the Cast made R trend of increase both norepinephrine (NE) and dopamine (DA) in plasma, but the epinephrine (Epi) was no-aitered. In Nal, a significant changes could not seen in plasma NE and DA both Int and Cast groups with a exception of slight increase of Epi in Int-group and that Cast was not effective on hypothalamic NE and Epi, but its DA seems a slight decreasing and that in Nal, hypothalamic NE and Epi decreased significantly in In&group, but trend of decrease was seen in Cast-group, and that hypothalamic DA was slight decreased in Cast-group but not in In&group and that in Nal, hypothalamic DA was not changed both Iut and Cast-groups, and that in hippocampus NE, Cast showed no changes and Nal treatment showed a significant increase only in Int group (2 > 1) but cot in Cast group. In female, lGiEwas not significant altered in Int by Nal, however a significant increase of NE was appeared in plasma, hippocampus, thalamus + mid-brain and hypothalamus in Cast by Nal. In Nal treatment, DA was significantly increased in plasma, hypothalamus but decreased in cerebral cortex in Int, and a tendency of increase in plasma and a significant increase in thalamus + mid-brain and hypothalamus were found in Cast. In conclusive remark as correlation between HP and hypothalamic NE in groups of castrated and noncastrated male SHR, when hypothalamic NE was increased, the BP showed lower value, in other words, while BP was increased with naloxone, hypothalamic NE decreased. However, though the pressor response by naloxone was significantly higher in Cast-group than that of In&group, the degree of decreasing was lower in the former, namely, sensitivity to antihypertensive action of hypothalamic NE was potentiated by castration. In female brain, lack of estrogen by castration provokes increase of intrinsic opiate and this accelerates the phenomenon of inhibitory action to CA release, however when Nal was administrated to Cast, actions of intrinsic opiate was blocked and, in consequence, the inhibitory action to CA was deprived and this lead to rising of CA (NE, DA)-induction.
I
P.lU.173
la-
Toorop,
G.P. and Jansen,
J.A.P.
Dept. of Pharmacology. Duphar B. V. P. 0. Box 900. 1380 DA Weesp, The Netherlandr
The centrally acting 5-HT,a agonists, 8-OH-DPAT and flesinoxan, reduce blood pressure and decrease heart rate in both anaesthetized and unanaesthetized animals via a decrease in sympathetic and an increase in vagal tone (Dreteler