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Title:The cardiovascular effects of the pharmacological interruption of the brain renin-angiotensin system in Dahl salt-induced hypertension
Author(s):Lark, Lisa Anne
Doctoral Committee Chair(s):Weyhenmeyer, James A.
Department / Program:Neuroscience
Discipline:Neuroscience
Degree Granting Institution:University of Illinois at Urbana-Champaign
Degree:Ph.D.
Genre:Dissertation
Subject(s):Biology, Neuroscience
Abstract:The brain renin-angiotensin system (RAS) is a known regulator of cardiovascular function. The present studies investigated the cardiovascular effects of the pharmacological interruption of this system in hypertensive inbred Dahl salt-sensitive (DS/JR) rats.
Intracerebroventricular (i.c.v.) administration of the angiotensin converting enzyme inhibitor captopril (10 $\mu$g) to conscious, freely moving DS/JR rats produced a sustained depressor response but was without effect in normotensive control inbred Dahl salt-resistant rats.
Remaining studies focused on the effects of centrally administered peptide and nonpeptide angiotensin II (ANG II) antagonists in DS/JR rats. Both the peptide antagonist sarthran (20 $\mu$g) and the nonpeptide antagonist losartan (10 $\mu$g), which is specific to the AT$\sb1$ receptor subtype, blocked pressor and dipsogenic responses to i.c.v. ANG II. The AT$\sb2$ receptor antagonist PD 123319 (10 $\mu$g) did not block the responses. Sarthran alone produced a significant and short-lived bradycardia with an accompanying slight depressor response. Losartan and PD 123319 were without effect on blood pressure and heart rate.
The sarthran-induced bradycardia was further evaluated by examining its magnitude after preblockade of one or both of the ANG II receptor subtypes. Both losartan and PD 123319 (10 $\mu$g) inhibited the bradycardic response to 20 $\mu$g of sarthran by about 45%. Preblockade of both sites resulted in a slightly greater inhibition suggesting that sarthran's effects are mediated interdependently by the AT$\sb1$ and AT$\sb2$ sites.
In summary, the present studies demonstrated that the brain RAS is involved in cardiovascular regulation in the DS/JR rat and, as such, may be a potential target for the treatment of salt-induced hypertension. Furthermore, evidence was presented which suggests that both ANG II receptor subtypes are involved in this function.
Issue Date:1994
Type:Text
Language:English
URI:http://hdl.handle.net/2142/21218
Rights Information:Copyright 1994 Lark, Lisa Anne
Date Available in IDEALS:2011-05-07
Identifier in Online Catalog:AAI9416390
OCLC Identifier:(UMI)AAI9416390


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