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

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.

Name dc:type.qualificationname

Ph.D.

Level dc:type.qualificationlevel

doctoral

Grantor dc:publisher.institution

Aston University

Year dc:date.issued

1975

Author dc:creator

• Cooling, M.J.