University of Illinois Urbana-Champaign

The cardiovascular effects of the pharmacological interruption of the brain renin-angiotensin system in Dahl salt-induced hypertension

Lark, Lisa Anne

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Description

Title
The cardiovascular effects of the pharmacological interruption of the brain renin-angiotensin system in Dahl salt-induced hypertension
Author(s)
Lark, Lisa Anne
Issue Date
1994
Doctoral Committee Chair(s)
Weyhenmeyer, James A.
Department of Study
Neuroscience
Discipline
Neuroscience
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Keyword(s)
Biology, Neuroscience
Language
eng
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.
Type of Resource
text
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http://hdl.handle.net/2142/21218
Copyright and License Information
Copyright 1994 Lark, Lisa Anne

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Graduate Dissertations and Theses at Illinois PRIMARY
Graduate Theses and Dissertations at Illinois
Dissertations - Neuroscience