The mechanisms involved in the responses elicited by intracerebroventricular administration of renin and angiotensin in the conscious cat

  • M.J. Cooling

Student thesis: Doctoral ThesisDoctor of Philosophy


Angiotensin II is an octapeptide formed by the action of the
enzyme renin on a glycoprotein substrate. It has potent pharmacological
effects on the central nervous system causing water drinking and
vasopressor responses. Recently enzyme systems capable of the
synthesis and destruction of angiotensin have been isolated from
brain tissue.

The cat does not readily drink water and drinking had not been
elicited by Wan CHAS ddd otha ion of drugs. This thesis describes
the dipsogenic effects of renin and angiotensin in the cat.
Intracerebroventricular (icv) administration of renin,
angiotensin I and II each induced drinking in the water-replete cat
and in addition angiotensin I and II were effective dipsogens when
given intravenously (iv).

Peptide inhibitors which horses block the synthesis or
biological action of angiotensin II were used to analyse these
dipsogenic effects. It was established that drinking caused by icv
renin and angiotensin I was mediated by angiotensin II. Drinking
elicited by iv angiotensin I or II was shown to be due to the action
of angiotensin II within the brain. The results also indicated that
systemic angiotensin I may be converted to angiotensin II in the brain.

The effects of angiotensin II may be mediated by release of
central neurotransmitters. This hypothesis was investigated using
autonomic blocking drugs. The evidence indicated that central
β-adrenoceptor or dopamine receptor mechanisms were involved.

Drinking behaviour in the cat was also elicited by administration
of hypertonic saline, polyethylene glycol or β -adrenoceptor agonists.
A preliminary study of the contribution of renin and angiotensin to these responses was made using a peptide inhibitor.

In the final chapter the centrally mediated vasopressor effects
of angiotensin II was studied in the conscious cat and rabbit. The
results obtained in the rabbit were interesting since they
Suggested that the response was mediated by release of a humoral
agent from the brain.
Date of Award1975
Original languageEnglish


  • intracerebroventricular administration
  • renin
  • angiotensin
  • conscious cat

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