Mechanism of action of angiotensin on intestinal transport

Upsher, Mary Elizabeth (1981) Mechanism of action of angiotensin on intestinal transport. University of Southampton, Doctoral Thesis.

Abstract

A preliminary study was carried out in an attempt to provide a better in vivo preparation in which to study the mechanism of action of angiotensin in its stimulation of fluid transport across the small intestine. 24 hour prior nephrectomy is shown to increase the sensitivity of the preparation to the hormone, but did not result in an increase in the magnitude of the maximum response. Investigations into the mechanism of action of angiotensin on intestinal fluid transfer were carried out to test the possibility that the hormone's action is mediated by noradrenaline released from adrenergic nerve endings innervating the mucosa. Both angiotensin and noradrenaline stimulate fluid transport, and the response to both agents is blocked by the antagonist phentolamine. Endogenous noradrenaline has been shown to mimic the actions of infused noradrenaline, in that the sympathomimetic amine tyramine enhances fluid transport in both normal and adrenalectomised animals in vivo, and the response is blocked by phentolamine. The response to angiotensin is lost with the destruction of catecholaminergic nerve fibres by pretreatment with 6-hydroxydopamine. The inability of angiotensin to enhance net absorption of sodium in the in vitro stripped sheet preparation, in conjunction with the inhibition of angiotensin's response in vivo by ganglion blockade, suggests that angiotensin may exert its action by enhancing the stimulus-evoked release of noradrenaline. The unresponsiveness of the in vitro preparation to angiotensin may also be due to depressed noradrenaline levels. Supporting this proposal, is the observation that, by raising these levels pharmacologically, a noradrenaline-like response is obtained with tyramine, which, under normal conditions, has no effect on this in vitro preparation. A possible involvement of dopamine in angiotensin's stimulation of intestinal transport in vivo, is suggested by the inhibition of the response by the dopamine antagonist sulpiride. It seems probable however, that any involvement of dopamine is due to its actions, as sulpiride also reduces noradrenaline-induced transport and the response to dopamine in the in vitro preparation is blocked by phentolamine.

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