Angiotensin (II) is an endogenous polypeptide involved in the control of blood pressure, heart rate and water balance. Receptive mechanisms for the central actions angiotensin are linked to the circumventricular organs, namely, the subfornical organ and the area postrema which characteristically lack the blood-brain barrier. The area postrema moreover contains the chemoreceptor trigger zone for vomiting which is activated by angiotensin. The primary aim of this proposal is to assess our hypothesis that the area postrema mediates a direct action of angiotensin on breathing as yet another functional element in the overall influence of this polypeptide on vital homeostasis. The postulated central respiratory action of angiotensin is to be revealed in two days: (1) by systemic administration after peripheral baro- and chemo-denervation, and (2) by intracerebroventricular administration. The effects of angiotensin on respiration will be characterized by transient and steady-state alterations in breathing pattern, CO2 responsiveness and central electrical excitability in anesthetized cats. We will test our hypothesis initially by making lesions of the area postrema in acute preparations. Disruption of angiotensin-induced respiratory effects will be confirmed in chronic preparations. Failing this, alternative central targets to be explored are receptive elements of the forebrain, the subnucleus medialis of the midbrain and the ventral chemosensitive surface of the medulla. These will be evaluated by means of brain transections, local electrolytic lesions and regional intra-arterial injections of angiotensin after ligation of the basilar artery. Concurrent observations will be made on cardiovascular effects of angiotensin for comparative analysis with the effects of respiration.
| Borison, H L; Hubbard, J I; McCarthy, L E (1988) Central respiratory inhibition by angiotensin II in anesthetized cats. J Pharmacol Exp Ther 247:781-90 |
