Functional involvement of angiotensin AT2 receptor in adrenal catecholamine secretion in vivo

被引:18
|
作者
Martineau, D
Lamouche, S
Briand, R
Yamaguchi, N
机构
[1] Univ Montreal, Fac Pharm, GRSNA, Montreal, PQ H3C 3J7, Canada
[2] Bristol Myers Squibb Canada, Montreal, PQ H4N 2M7, Canada
关键词
AT(1) and AT(2) subtypes; PD; 123319; CGP; 42112; AT(2) antagonist; anesthetized dog;
D O I
10.1139/cjpp-77-5-367
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The aim of the present study was to analyse modulations of adrenal catecholamine secretion from the adrenal gland of anesthetized dogs in response to locally administered angiotensin II (AngII) in the presence of either PD 123319 or CGP 42112, both of which are highly specific and selective ligands to angiotensin AT(2) receptor. Plasma concentrations of epinephrine and norepinephrine in adrenal venous and aortic blood were quantified by a high performance liquid chromatography coupled with electrochemical detection (HPLC-EC) method. Adrenal venous blood flow was measured by gravimetry. Local administration of AngII (0.05 mu g, 0.1 mu M) to the left adrenal gland increased adrenal gland catecholamine output more than 30 times that found in nonstimulated states. Administration of either PD 123319 (0.085 mu g (0.23 mu M) to 8.5 mu g (23 mu M)) or CGP 42112 (0.005 mu g (0.01 mu M) to 5 mu g (10 mu M)) did not affect the basal catecholamine output significantly. The increase in adrenal catecholamine output in response to AngII was inhibited by similar to 80% following the largest dose of PD 123319. CGP 42112 significantly attenuated the catecholamine response to AngII by similar to 70%. PD 123319 and CGP 42112 were devoid of any agonist actions with respect to catecholamine output by the adrenal gland in vivo. Furthermore, both PD 123319 and CGP 42112 inhibited the increase in adrenal catecholamine secretion induced by local administration of AngII. The present study suggests that AT(2) receptors play a role in mediating catecholamine secretion by the adrenal medulla in response to AngII receptor agonist administration in vivo.
引用
收藏
页码:367 / 374
页数:8
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