mise à jour du
13 septembre 2009
J. Physiol
Drinking induced by injections of angiotensin
into forebrain and mid-brain sites of the monkey
LG Sharpe, LW Swanson
Department of Psychiatry, Washington University School of Medicine
St Louis, Missouri, U.S.A.


1. Unilateral and bilateral injections of 1.0 pl. solutions of angiotensin II into specific brain sites produced copious drinking of water in the waterreplete rhesus monkey (Mactwa mulatta).
2. Of six brain regions in seven monkeys into which a total of 368 microinjections of angiotensin II were made, three were sensitive to angiotensin II. In decreasing order of sensitivity, they were (i) a rostral zone that included the septum, the anterior hypothalamus and the preoptic region, (ii) a caudal zone consisting of the mesencephalic central grey, and (iii) the lateral and third ventricles near the foramen of Monro. Of the regions tested, those that were relatively inactive included (i) the mid line thalmus, (ii) the mid-brain reticular formation, and (iii) metencephalic points in the cerebellum, the 4th ventricle and the dorsal aspect of the pons.
3. Bilateral microinjections of angiotensin II into the sensitive regions in doses as low as 0•75-6 ng were dipsogenic and, with increasing doses, drinking occurred in a dose-dependent fashion up to 500 ng, after which the amount drunk levelled off or was reduced. The dose-response curve for unilateral microinjections began at 12•5 ng, and at doses higher than 50 ng unilateral and bilateral microinjections were equipotent.
4. The onset of drinking (without eating) averaged 21-3•2 min following the end of microinjections for all sensitive tissue sites. Injections into the ventricles produced significantly longer drinking latencies.
5. Angiotensin I elicited drinking in amounts comparable to angiotensin II at a dose of 100 ng whereas analogues of angiotensin II were weak dipsogens. Of the three analogues tested, Phe4, Tyr5-angiotensin II was the most potent dipsogen, followed by 11e5-angiotensin II. The 1-7 heptapeptide, des-Phe5-angiotensin II was an ineffective dipsogen. Carbachol mieroinjected into the most sensitive angiotensin drinking sites had no dipsogenic action in the water-replete monkey.
6. Tachyphylaxis to angiotensin II was demonstrated as a reduction in mean water intake of 55 and 74 per cent on the second and third microinjections, respectively. This reduction appeared to be due to dilutional inhibition or signals from the amount of water ingested on the first microinjection of angiotensin II.
7. Monkeys drank an amount equal to a normal daily intake following two to three microinjections of angiotensin II in doses of 100-250 ng into sensitive regions. This extra water load caused no reductions in normal daily water intake either for the remainder of the experimental day or 24 hr later.
8. Pre-treatments with microinjections of an angiotensin-converting enzyme inhibitor, SQ 20,881, did not reduce the dipsogenic action of angiotensin I, suggesting that this and perhaps other peptide precursors act directly on receptor mechanisms to produce thinking. Attempts to change the polydipsic effects of angiotensin II were unsuccessful with pre-treatments of intracranial microinjections of either haloperidol, Jle8-angiotensin II or carbachol.
9. Microinjections of angiotensin II dissolved in hypertonic saline solutions had no influence on water intake when compared with the same dose dissolved in distilled water or isotonic saline.
10. Yawning was the only response besides drinking that appeared to be directly related to intracranial injections of angiotensin II in the monkey. The response appeared to be spontaneous, reflexive and dose-related, but did not seem to be related to the occurrence of sleep or to the stimulation of active drinking sites. The onset of yawning was within 5 min of the microinjection if no drinking occurred, or if non-drinking sites were stimulated with angiotensin II. Inasmuch as other injected substances have not elicited yawning, the significance of the angiotensin-yawning relation is unclear. In some instances, a hyperactive state of the animal followed intraventricular injections of angiotensin II. In other instances, intracranial microinjections of angiotensin II were followed by quietude or e.e.g. and behavioural signs of light sleep.
11. This work further confirms the findings of previous research which showed that angiotensin II is the most potent dipsogen in all species tested to date. This endogenous peptide appears to participate in natural thirst by acting on central mechanisms of extracellular thirst.