Proceedings of The Physiological Society
University of Oxford (2011) Proc Physiol Soc 23, PC221
Effects of the CB1 cannabinoid receptor on fluid intake and hormone secretion induced by water restriction
S. Ruginsk1, F. M. Vechiato2, J. Antunes-Rodrigues1, L. L. Elias1
1. School of Medicine of Ribeirao Preto, Ribeirao Preto, Sao Paulo, Brazil. 2. School of Nursing of Riberiao Preto, Ribeirao Preto, Sao Paulo, Brazil.
The endocannabinoid system participates in several homeostatic mechanisms, being the CB1 cannabinoid receptor (CB1R) the main subtype involved in the regulation of body fluid homeostasis. This study evaluated the effects of pretreatment with AM251, a CB1R antagonist, on fluid intake and hormone secretion in response to water restriction (WR). Male Wistar rats (n=5-13) had water but not food removed 24 hours (h) before the experiment. AM251 (3mg/Kg/1.5ml, or vehicle, 5% ethanol in 0.9% NaCl) was intraperitonially administered 30 minutes (min) before fluids were presented. The first group of animals had water and 1.8% NaCl intakes assessed in intervals for 2h after fluid presentation. In another group of animals, plasma concentrations of vasopressin (AVP), oxytocin (OT), atrial natriuretic peptide (ANP), angiotensin II (ANGII) and sodium were determined from trunk blood, which was obtained by decapitation immediately before fluids presentation. WR induced a significant increase in both water (0.34±0.26 vs. 2.79±0.77 ml/100g of body weight (b.w.), p<0.05, t=20 min) and 1.8% NaCl intake (0.01±0.01 vs 1.98±0.55 ml/100g of b.w., p<0.01, t=20 min), as well as in plasma sodium concentrations (135.28±1.40 vs 144.00±0.93 mEq/l, p<0.001). WR also increased OT (1.47±0.19 vs 5.18±0.61pg/ml, p<0.001) and AVP secretion (1.35±0.12 vs 7.57±0.94 pg/ml, p<0.001), although no significant changes were observed in ANGII circulating levels after the same stimulus. On the other hand, WR significantly decreased ANP plasma concentrations (55.54±9.10 vs 17.54±4.36 pg/ml, p<0.001). Previous administration of AM251 significantly reduced 1.8% NaCl ingestion induced by WR (3.18±0.75 vs 1.58±0.47 ml/100g of b.w., p<0.01, t=60 min), but it did not alter the effects of WR on water intake. Furthermore, AM251 further increased plasma sodium concentrations in WR rats (144.00±0.93 vs 150.00±1.83 mEq/l, p<0.05). Pretreatment with AM251 potentiated OT secretion in euhydrated (1.47±0.19 vs 2.92±0.51 pg/ml, p<0.05) but not in WR rats; no additional changes were produced by AM251 in AVP secretion induced by WR. On the other hand, previous administration of AM251 significantly enhanced ANGII secretion induced by WR (18.68±3.91 vs 240.16±34.40 pg/ml, p<0.001) and induced a further decrease in ANP secretion in euhydrated (55.54±9.10 vs 27.53±4.18 pg/ml, p<0.001) but not in WR rats. These data suggest that the CB1R: 1) participates in the control of sodium intake; 2) modulates neurohypophyseal hormone secretion; 3) regulates the secretion of peripheral hormones (ANGII and ANP).
Where applicable, experiments conform with Society ethical requirements