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1.
Peptides ; 17(1): 93-9, 1996.
Article in English | MEDLINE | ID: mdl-8822516

ABSTRACT

To characterize the urinary kinetics of AVP, and the influence of regional blood flow on the metabolic degradation of AVP, multiple doses of AVP were administered to conscious rabbits. AVP systemic clearance (ClT) was not influenced by changes in dose, in spite of a decrease in AVP urinary clearance following the highest dose. Hepatic blood flow was inversely associated with AVP concentrations, and despite a decrease in hepatic plasma flow of 37% (p < 0.05), following the high dose of AVP, ClT remained unchanged. These results indicate that AVP plasma kinetics are first order and plasma flow independent, and urinary kinetics are zero order.


Subject(s)
Arginine Vasopressin/blood , Arginine Vasopressin/urine , Animals , Arginine Vasopressin/administration & dosage , Biotransformation , Injections, Intravenous , Kinetics , Liver Circulation , Male , Rabbits , Regional Blood Flow , Renal Circulation
2.
Br J Pharmacol ; 113(1): 317-23, 1994 Sep.
Article in English | MEDLINE | ID: mdl-7812627

ABSTRACT

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.


Subject(s)
Dehydration/metabolism , Lidocaine/pharmacokinetics , Animals , Arginine Vasopressin/blood , Arginine Vasopressin/physiology , Atrial Natriuretic Factor/blood , Dinoprostone/urine , Lidocaine/analogs & derivatives , Lidocaine/blood , Male , Osmolar Concentration , Plasma Volume/physiology , Rabbits , Renin/blood
3.
Pharmacology ; 43(5): 282-92, 1991.
Article in English | MEDLINE | ID: mdl-1784627

ABSTRACT

The influence of dietary sodium and saralasin on the natriuretic and diuretic response to furosemide (5 mg/kg i.v.) was studied in three groups of conscious rabbits maintained for 4 weeks on either a normal sodium diet (NSD), or a low sodium diet (LSD) or a high sodium diet (HSD). Neither the sodium content in the diet nor saralasin affected glomerular filtration rate or renal plasma flow. Compared to the NSD, an LSD did not affect the furosemide-induced increment in urinary excretion of sodium (dUNaV) but increased the increment in urinary excretion (dUV) (p less than 0.05). An HSD reduced the furosemide-induced dUNaV and dUV (p less than 0.05). Plasma renin activity (PRA) increased following furosemide administration in animals on an NSD and an LSD, but not in those on an HSD. Independent of diet, a positive correlation occurred between the increment in PRA and the dUNaV (p less than 0.001). Saralasin increased PRA and decreased baseline urinary excretion of sodium (UNaV). In addition, in rabbits on an LSD, saralasin reduced the furosemide-induced dUNaV and dUV by 34 and 27% (p less than 0.05), respectively. It is concluded that furosemide-induced diuresis is increased in rabbits on an LSD and decreased in rabbits on an HSD. In animals on an LSD, the increase in furosemide response appears to be associated with changes in the activity of the renin-angiotensin system and in rabbits on an HSD, the decrease in furosemide effect is probably the net result of several factors.


Subject(s)
Diuresis/drug effects , Furosemide/pharmacokinetics , Natriuresis/drug effects , Saralasin/pharmacology , Sodium, Dietary/pharmacology , Animals , Dinoprostone/urine , Glomerular Filtration Rate/drug effects , Male , Rabbits , Radioimmunoassay , Renal Circulation/drug effects , Renin/blood , Sodium/urine , Water-Electrolyte Balance/drug effects
4.
Clin Invest Med ; 10(4): 350-4, 1987 Jul.
Article in English | MEDLINE | ID: mdl-2958203

ABSTRACT

Atrial natriuretic factor, plasma renin activity, and plasma vasopressin were measured in 38 patients with chronic renal failure prior to and after hemodialysis. The objective of the study was to evaluate the effect of acute volume changes on the level of atrial natriuretic factor. Blood pressure prior to dialysis was 154 +/-/83 +/- mmHg, and 132 +/-/78 +/- mmHg post dialysis (p less than 0.005) while heart rate increased from 82.5 +/- 1.8 beats per minute to 91.2 +/- 2.4 after dialysis (p less than 0.005). The average weight of patients was reduced from 60.2 +/- 2.4 kg to 57.8 +/- 2.4 kg (p less than 0.005). While the plasma levels of atrial natriuretic factor in normal individuals were 65.3 +/- 2.9 pg/ml (n = 59), these levels were 251.4 +/- 28 pg/ml prior to dialysis in the patients with renal failure, and 173.3 +/- 18.0 pg/ml after dialysis (p less than 0.005). Twenty-nine patients had a reduction in the levels of this atrial natriuretic factor, 5 had no change, and 4 had an increase. The atrial factor was not detected in the dialysate fluid of 6 patients in whom it was measured. Peripheral renin values were unchanged from 2.12 +/- 0.68 to 2.07 +/- 0.8 ng/ml/hr. Plasma vasopressin before dialysis was significantly higher than normal, and increased from 7.04 +/- 0.56 to 9.95 +/- 1.55 pg/ml following dialysis (p less than 0.05). The changes in atrial natriuretic factor values correlated most significantly (r = 0.47, p less than 0.005) with the changes in weight, but no single variable could explain the changes in atrial natriuretic factor.


Subject(s)
Atrial Natriuretic Factor/blood , Kidney Failure, Chronic/blood , Renal Dialysis , Adult , Aged , Blood Pressure , Female , Humans , Kidney Failure, Chronic/therapy , Male , Middle Aged , Pulse , Renin/blood , Vasopressins/blood
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