St Lambert, Jane Helen Denise; (1996) The role of adenosine, at the level of the nucleus tractus solitarii, in the hypothalamic defence response. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Adenosine has been implicated in having a neuromodulatory role in cardiovascular control at the level of the oblongata. Pharmacological techniques have been employed to study the possible involvement of adenosine A1 in the caudal nucleus tractus solitarii (cNTS) in mediating the cardiovascular response evoked during hypothalamic defence area (HDA) stimulation. The location of A1 binding sites in the rat and cat medulla and forebrain was investigated autoradiographically using [3H] 1, 3-diproyl-8-cyclopentylxanthine. Relatively high levels of binding was observed in the rostral ventrolateral medulla and cNTS whilst the hypothalamus was relatively devoid of adenosine A1 binding sites. Non-specific binding was extremely low, indicating that binding was to adenosine A1 receptors. Stimulation of the HDA elicits a pattern of cardiovascular response which include an a biphasic increase in blood pressure an accompanying tachycardia. In the anaesthetised and artificially ventilated rat, intravenous and intracerebroventricular injections of a selective adenosine A1 antagonist attenuated the biphasic pressor response evoked during HDA stimulation. In contrast, a polar antagonist, which does not cross the blood brain barrier, had no effect on the evoked response. These results indicated that adenosine A1 receptors, located within the CNS, are activated during the defence response. Microinjections of adenosine were made into discrete regions of the cNTS to determine whether this nucleus was involved in mediating the cardiovascular response evoked during HDA stimulation. Microinjections of 50 nl adenosine into the cNTS evoked 2 patterns of haemodynamic responses and augmented the biphasic pressor response elicited on HDA stimulation. By contrast, microinjections of adenosine antagonists into this area attenuated the pressor response. In order to ascertain if the adenosine released during HDA stimulation was derived from ATP metabolism an 5'ectonucleotidase inhibitor, α,βmethylene adenosine diphosphate (α,βmeADP) was micro injected into the cNTS. α,βmeADP attenuated predominantly the primary rise in blood pressure evoked during HDA stimulation. It is concluded that adenosine A1 receptors, located within the cNTS, may be involved mediating the cardiovascular changes associated with the hypothalamic defence response. In addition, one of the sources of adenosine involved in the defence response is ATP.

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