Ghrelin reduces hypertonic saline intake in a variety of natriorexigenic conditions

Abstract

Ghrelin is a gut peptide that has been studied extensively for its role in food intake and energy balance. More recent studies show that ghrelin reduces water intake in rats and some non-mammalian species. Despite the importance of the regulation of NaCl intake in body fluid homeostasis, the effects of ghrelin on saline intake have not been investigated. Accordingly, we tested the effect of ghrelin on water and 1.8% NaCl intake in two-bottle test conditions with the following five stimuli that increase hypertonic saline intake: central angiotensin II administration; 24 h fluid deprivation; water deprivation followed by partial rehydration; dietary sodium deficiency; and polyethylene glycol administration combined with dietary sodium deficiency. We found that ghrelin attenuated saline intake stimulated by angiotensin II, by water deprivation followed by partial rehydration and by dietary sodium deficiency. We did not detect an effect of ghrelin on saline intake after 24 h fluid deprivation without partial rehydration or after the combination of polyethylene glycol and dietary sodium deficiency. The finding that ghrelin reduced hypertonic saline intake in some, but not all, natriorexigenic conditions mirrors the previously published findings that in one-bottle tests of drinking, ghrelin reduces water intake in only some conditions. The results provide evidence for a new role for ghrelin in the regulation of body fluid homeostasis.

Figure 1

Effect of ghrelin on water, 1.8% NaCl, and food intakes after I.C.V. administration of AngII when food was available during fluid intake testing (Experiment 1A). In a 4 h test, ghrelin reduced 30-min saline intake (A) but had no effect on non-cumulative water intake (B). Total saline intake and total fluid intake were also attenuated in ghrelin-treated rats (C). Ghrelin reliably stimulated food intake (D). In Panel C, groups of vehicle- and ghrelin-treated rats are respectively abbreviated “Veh” and “Ghr.” All data are shown as mean ± SEM (n=5–6 per treatment group) and asterisks indicate p<0.05 compared to controls.

Figure 2

Effect of ghrelin on water, 1.8% NaCl, and food intakes after I.C.V. administration of AngII when food was not available during fluid intake testing (Experiment 1B). In a 2 h fluid intake test, ghrelin reduced 15-min intake of hypertonic saline (A) but had no effect on AngII-induced water intake (B). Total fluid intake was unaffected by ghrelin (C). When food was returned to the cage after the fluid intake test, ghrelin-treated rats ate more food than did vehicle-treated rats (D). In Panel C, groups of vehicle- and ghrelin-treated rats are respectively abbreviated “Veh” and “Ghr.” All data are shown as mean ± SEM (n=4–6 per treatment group) and asterisks indicate p<0.05 compared to controls.

Figure 3

Effect of ghrelin on water, 1.8% NaCl, and food intakes after 24 h fluid deprivation when food was available during fluid intake testing (Experiment 2A). Ghrelin had no effect on non-cumulative saline (A) or water (B) intake, but total 4 h fluid intake was increased in ghrelin-treated rats (C). Food intake was increased by ghrelin (D). In Panel C, groups of vehicle- and ghrelin-treated rats are respectively abbreviated “Veh” and “Ghr.” All data are shown as mean ± SEM (n=7 per treatment group) and asterisks indicate p<0.05 compared to controls.

Figure 4

Effect of ghrelin on water, 1.8% NaCl, and food intakes after 24 h fluid deprivation when food is not available during fluid intake testing (Experiment 2B). Ghrelin had no effect on non-cumulative saline (A) or water (B) intake during a 2 h fluid intake test, but total 2 h fluid intake was reduced by ghrelin, primarily due to a statistically significant reduction in water intake (C). When food was made available after fluid intake testing, ghrelin reliably increased food intake (D). In Panel C, groups of vehicle- and ghrelin-treated rats are respectively abbreviated “Veh” and “Ghr.” All data are shown as mean ± SEM (n=6–9 per treatment group) and asterisks indicate p<0.05 compared to controls.

Figure 5

Effect of ghrelin on water, 1.8% NaCl, and food intakes after WD-PR (Experiment 3). There were no differences between groups in water intake during the partial rehydration phase (A). During a 2 h fluid intake test, ghrelin reduced saline intake at 15 min (B) and reduced non-cumulative water intake from 15–30 min (C). Total 2 h fluid intake was also reduced by ghrelin (D). When food was returned to the cage, ghrelin-treated rats ate more food than did vehicle-treated rats (E). In Panel D, groups of vehicle- and ghrelin-treated rats are respectively abbreviated “Veh” and “Ghr.” All data are shown as mean ± SEM (n=5–8 per treatment group) and asterisks indicate p<0.05 compared to controls.

Figure 6

Effect of ghrelin on water, 1.8% NaCl, and sodium-deficient diet intakes after dietary sodium deficiency (Experiment 4). Ghrelin had no effect on binned saline (A) or water (B) intake, but total 2 h saline intake was reduced in ghrelin-treated rats (C). When sodium-deficient diet was made available after the fluid intake test, ghrelin-treated rats consumed more food than did vehicle-treated rats (D). In Panel C, groups of vehicle- and ghrelin-treated rats are respectively abbreviated “Veh” and “Ghr.” All data are shown as mean ± SEM (n=9–10 per treatment group) and asterisks indicate p<0.05 compared to controls.

Figure 7

Effect of ghrelin on water, 1.8% NaCl, and sodium-deficient diet intakes after PEG treatment plus dietary sodium deficiency (Experiment 5). Ghrelin had no effect on non-cumulative intake of hypertonic saline (A), but increased non-cumulative water intake at 15 min (B). Ghrelin had no effect on total 2 h fluid intake (C). Ghrelin reliably increased food intake (D). In Panel C, groups of vehicle- and ghrelin-treated rats are respectively abbreviated “Veh” and “Ghr.” All data are shown as mean ± SEM (n=7–9 per treatment group) and asterisks indicate p<0.05 compared to controls.