Gut-brain signaling of water absorption inhibits vasopressin in rats.

The mechanism for inhibition of vasopressin (AVP) by gastric water infusion was examined in 24- or 48-h dehydrated conscious rats (n = 136 rats, 255 experiments; mean AVP baseline = 6.3 pg/ml). Gastric water infusions of 1 (n = 8), 2.5 (n = 19), and 4 ml (n = 10) caused a volume-dependent inhibition of plasma AVP by -0.31, -1.77*, and -3.02* pg/ml, with decreases of systemic osmolality of -1.06, -1.52, and -4.26* mosmol/kgH2O (* = significant vs. isotonic, Duncan's test). Gastric isotonic infusions (1-4 ml) had no effect or slightly increased AVP. Systemic infusions of 1.25 (n = 6), 2.1 (n = 10), and 6.3 ml (n = 8) inhibited AVP by -0.48, -1.07, and -2.51 pg/ml, with decreases in systemic osmolality of -1.61, -2.77*, and -7.21* mosmol/kgH2O. Systemic isotonic infusions (2.1 and 6.3 ml) slightly inhibited AVP by -0.71 and -0.85 pg/ml. Individual changes in AVP by gastric infusion of 2.5 ml of water did not correlate with changes in systemic osmolality, mean arterial pressure, or heart rate but highly correlated with preinfusion AVP (r = 0.74, P < 0.0001, n = 28). Pretreatment with systemic atropine methyl bromate (0.7 mg/rat), which abolishes the AVP secretion to gastric hypertonic saline, did not affect the AVP response to gastric water infusion (n = 9). Combination of 2.5 ml of gastric water and systemic hypertonic saline prevented the decrease in systemic osmolality and still significantly inhibited plasma AVP. Maximal inhibition of AVP by gastric water was reduced by 62.6% after lesion of the common hepatic vagal branch (n = 5) relative to shams with identical abdominal surgery (n = 6) and by 62.7 and 72.5% after right (n = 11) and left (n = 8) cervical vagotomy relative to 12 shams (P < 0.05). The results show that 1) gastric water absorption is signaled mainly by splanchnic osmosensors, 2) water signaling is atropine insensitive, and 3) the major water-signaling pathway projects through the common hepatic vagal branch and cervical vagal nerves.