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Effects of intracerebroventricular losartan on angiotensin II‐mediated pressor responses and c‐fos expression in near‐term ovine fetus
Author(s) -
Shi Lijun,
Mao Caiping,
Thornton Simon N.,
Sun Wanping,
Wu Jiawei,
Yao Jiaming,
Xu Zhice
Publication year - 2005
Publication title -
journal of comparative neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.855
H-Index - 209
eISSN - 1096-9861
pISSN - 0021-9967
DOI - 10.1002/cne.20802
Subject(s) - losartan , subfornical organ , endocrinology , medicine , angiotensin ii , median preoptic nucleus , angiotensin ii receptor type 1 , circumventricular organs , lateral parabrachial nucleus , renin–angiotensin system , lamina terminalis , biology , hypothalamus , receptor , parabrachial nucleus , blood pressure
The renin‐angiotensin system plays an important role in cardiovascular control. Intracerebroventricular (i.c.v.) angiotensin (ANG) II causes a reliable pressor response in the fetus at 90% gestation. To determine the roles of brain AT 1 and AT 2 receptors in this response, the effects of the central AT 1 and AT 2 receptor antagonists losartan and PD123319 were investigated in chronically prepared near‐term ovine fetuses. Losartan at 0.5 mg/kg (i.c.v.) abolished central ANG II‐induced pressor responses. High‐dose losartan (5 mg/kg, i.c.v.) showed a potentiation of the pressor response to i.c.v. ANG II, accompanied by bradycardia. Associated with the pressor responses, c‐fos expression in the cardiovascular controlling areas was significantly different between the low and high doses of losartan. These areas included the subfornical organ, median preoptic nucleus, organum vasculosum of the lamina terminalis, and paraventricular nuclei in the forebrain, and the tractus solitarius nuclei, lateral parabrachial nuclei in the hindbrain. Low‐dose losartan markedly reduced c‐fos in these areas after i.c.v. ANG II, while the high‐dose losartan together with ANG II elicited a much stronger FOS‐immunoreactivity in these areas than that induced by i.c.v. ANG II alone. This is a novel finding, that c‐fos expression in the brain can be both activated and inhibited under the same condition. Central ANG II‐induced fetal pressor responses were not altered by PD123319 (0.8 mg/kg). These results indicate that i.c.v. losartan at a high and a low dose has strikingly different effects on central ANG II‐induced pressor responses in fetuses at late gestation, and that the AT 1 mechanism plays an important role in fetal cardiovascular regulation. J. Comp. Neurol. 493:571–579, 2005. © 2005 Wiley‐Liss, Inc.