Subfornical organ lesions reduce intravenous angiotensin-induced drinking.

A competitive angiotensin converting enzyme antagonist SQ 20, 881 (SQ), was used to examine the role of the renin-angiotensin system in putative renin-dependent thirst in the albino rat. Significant enhancement of "renin-dependent" as well as renin-independent drinking was observed in the presence of peripheral SQ. Intraventricular SQ obviated this enhancement of drinking but did not affect the water intake caused by the original stimulus itself, whereas it sharply reduced drinking evoked by peripheral renin in nephrectomized rats. Prior renin depletion likewise had no influence on so-called renin-dependent thirst.

https://science.sciencemag.org/content/sci/182/4116/1031.full.pdf

Renin-Angiotensin Role in Thirst: Paradoxical Enhancement of Drinking by Angiotensin Converting Enzyme Inhibitor

The brain is known to contain many peptides of diverse molecular weight and complexity. The larger ones contribute to the structure and to the enzymatic machinery essential for the metabolism of this complex organ. Smaller ones are hormones and some may be involved in the formation of long-term memory. Still others may arise as a consequence of generalized experiences such as sleep. Because the number of possible amino acid combinations is immense, it is likely that many more peptides will be discovered and that these will be found to have functions unique to the brain.

Peptides and the Central Nervous System

Angiotensin and thirst: studies with a converting enzyme inhibitor and a receptor antagonist.

In 7 unanesthetized rhesus monkeys (Macaca mulatta), spontaneous drinking was measured following a 1 μl injection of nicotine at 153 sites in the hypothalamus and mesencephalon. Nicotine in doses of 5 and 10 μg evoked the intake of water in volumes ranging from 35–365 ml within 30 min following the microinjection. A lower dose produced less drinking or had no effect. An anatomical mapping of this response revealed that nicotine exerted its dipsogenic effect at only 18 of the 153 sites at which the alkaloid was injected. These sensitive loci were clustered in and around the mammillary complex. When 1 μl of angiotensin II solution was microinjected in a dose of 1 μg at homologous sites in the hypothalamus and mesencephalon, volumes of water from 30–320 ml were consumed within 30 min after the injection. The anatomical distribution of the loci sensitive to angiotensin correspond identically to the nicotine drinking sites, i.e., the region surrounding the mammillary bodies and extending caudally into the mesencephalon. It was hypothesized that a cholinergic pathway mediated by nicotine receptors may subserve a drinking circuit in the brain stem of the primate. Further, because of the anatomical concordance of the dipsogenic substances, it was proposed that topically applied angiotensin may act to release acetylcholine within this region.

Drinking in the monkey evoked by nicotine or angiotensin II microinjected in hypothalamic and mesencephalic sites

1. Intravenous injection of five Goldblatt units (Gbl.U) of renin, or intravenous infusion of 2.5 mug of angiotensin into nephrectomized rats decreased plasma volume by 22 +/- 2% (calculated from the increase of the haematocrit) or by 14 +/- 2% (calculated from the increase in protein concentration) within 2 minutes. Fifteen minutes and 60 min after injection or infusion, the plasma volume (calculated from both parameters) was still 10% lower than initially.2. The initial discrepancy between haematocrit values and plasma protein concentration was neither due to mobilization of red blood cells (r.b.c.) from the spleen, nor to an increase in r.b.c. volume.3. The observed decrease in plasma volume was large enough to explain the drinking response to renin and angiotensin. Renin may thus induce or aggravate hypovolaemia rather than signalling its occurrence to hypothalamic receptors.

Lisette Haefeli

Papers

Induction of hypovolaemia by thirst-inducing doses of renin or angiotensin II.