Proceedings of The Physiological Society
University of Manchester (2010) Proc Physiol Soc 19, PC249
Enhanced vasopressin-induced natriuresis in rats exposed to a low protein diet in utero
M. A. Haley1, S. H. Alwasel2, N. Ashton1
1. Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom. 2. Fetal Programming of Diseases Research Chair, King Saud University, Riyadh, Saudi Arabia.
Table 1. Glomerular filtration, urine flow and sodium excretion rates in 4 week old control (n = 7 litters) and low protein rats (n = 7 litters) after 30 mins infusion of vehicle or AVP (µU/min). Data shown as mean ± SEM. * P <0.05 vs vehicle; † P <0.05 C vs LP receiving similar treatment, oneway ANOVA and Duncan’s test
Rats born to mothers who were fed a low protein (LP) diet during pregnancy develop hypertension and have impaired renal function (1). We have reported previously that young LP rats have higher urine flow rates and excrete more sodium than controls under euvolaemic conditions (1). As young rats are known to be resistant to the antidiuretic actions of vasopressin (AVP) (2) the aim of this study was to determine the effect of exogenous AVP on renal function in young LP rats. Pregnant Wistar rats were fed semi-synthetic diets containing either 9% (low, LP, n = 7) or 18% (control, C, n = 7) protein from conception until birth. Thereafter dams and pups received standard chow. At 4 weeks of age, Inactin-anaesthetised (100 mg/Kg ip) male pups were prepared for renal clearance measurements (1). Vehicle (0.154 M NaCl) was infused at 40 µl/min over a 2 h equilibration period after which baseline measurements were made for 1 h. Rats were then divided randomly into groups which received either vehicle (0.154 M NaCl), AVP at 24 µU/min or AVP at 120 µU/min for 1 h (1 µU = 2.2 pg). Mean arterial pressure was higher in LP rats compared with controls (102 ± 5 vs 88 ± 3 mmHg P < 0.05). Glomerular filtration rate (GFR) was unaffected in either group by AVP treatment (Table 1). Urine flow rate (V) tended to increase in LP rats during AVP infusion at 24 µU/min but this was not statistically significant; however when AVP was infused at 120 µU/min urine flow rate increased in both control and LP rats. Total (UNaV) and fractional excretion (FENa) of sodium were increased by AVP at both 24 and 120 µU/min in LP rats; total sodium excretion was only increased in control rats during AVP infusion at 120 µU/min. The unexpected diuresis following AVP infusion may be explained by the resistance of immature rats to AVP. Phosphodiesterase activity is increased in young rats so that, despite activation of adenylate cyclase via the V2 receptor, cAMP is diminished (2). The diuresis appears to be osmotically induced as a result of AVP-induced natriuresis. LP rats are more sensitive to the natriuretic actions of AVP which may explain our prior observations of higher urine flow rates in LP rats (1).
Where applicable, experiments conform with Society ethical requirements