1. The present study aimed to investigate the effect of
dehydration and hyperosmolal hydration on the disposition of
lignocaine and two of its metabolites,
monoethylglycinexylidide (
MEGX) and
glycinexylidide (GX). 2.
Lignocaine was infused to three groups of conscious rabbits: controls, rabbits previously deprived of water for 48 h and rabbits receiving an infusion of 2.5% NaCl. 3. In dehydrated and hyperosmolal-hydrated rabbits, plasma osmolality was 321 +/- 1 and 313 +/- 1 mOsm kg-1, respectively (P < 0.01 compared to controls, 285 +/- 1 mOsm kg-1). In dehydrated animals, baseline values of plasma
arginine vasopressin (AVP) concentrations and plasma
renin activity (PRA) were higher than in controls, i.e. 12.4 +/- 1.4 pg ml-1 and 15.4 +/- 1.7 ng AI ml-1 h-1 vs. 3.4 +/- 0.2 pg ml-1 (P < 0.01), and 5.1 +/- 0.6 ng AI ml-1 h-1 (P < 0.01), respectively;
atrial natriuretic peptide (
ANP) decreased from 55 +/- 11 to 32 +/- 4 pg ml-1 (P < 0.05). Compared to controls, hyperosmolal hydration only increased AVP to 15.5 +/- 0.7 pg ml-1 (P < 0.01). 4. Under both experimental conditions,
lignocaine plasma concentrations were almost double (P < 0.01) those in controls, due to a lower systemic clearance, e.g. 54 +/- 3 and 59 +/- 1 vs. 96 +/- 5 ml min-1 kg-1, respectively. Plasma levels of
MEGX increased (P < 0.01) only in dehydrated animals, although GX plasma concentrations were augmented (P < 0.01) about three fold in both groups of animals. The changes in
lignocaine plasma concentrations were correlated with AVP levels (R2 = 0.5168, P<0.001).5. To document the effect of AVP on hepatic plasma flow, another group of rabbits received on separate occasions two doses of AVP (17 and 84 ng kg-1) while receiving an infusion of in docyanine green. AVP reduced hepatic plasma flow from 38.9 +/-2.7 ml min-1 to 19.6 +/-2.5 ml min-1 (P<0.01).The predicted maximal AVP-induced decrease in hepatic plasma flow was 19.6 ml min-1 kg- 1(Emax), and AVP concentration eliciting 50% of Em.. (ED50) was 28.7 pg ml-1.6 It is concluded that both
dehydration and hyperosmolal hydration alter the disposition of
lignocaine and two of its metabolites.