Increased glomerular angiotensin II binding in rats exposed to a maternal low protein diet in utero.
In the rat, protein restriction during pregnancy increases offspring blood pressure by 20-30 mmHg. We have shown in an earlier study that this is associated with a reduction in nephron number and increased glomerular sensitivity to angiotensin II (Ang II) in vivo. Hence, we hypothesized that exposure to a maternal low-protein diet increases glomerular Ang II AT1 receptor expression and decreases AT2 receptor expression. To test this hypothesis, pregnant Wistar rats were fed isocalorific diets containing either 18% (control) or 9% (LP) protein from conception until birth. At 4 weeks of age, the kidneys of male offspring were harvested to measure cortical AT1 and AT2 receptor expression, 125I-Ang II glomerular binding, tissue renin activity, tissue Ang II and plasma aldosterone concentrations. AT1 receptor expression was increased (62%) and AT2 expression was decreased (35%) in LP rats. Maximum 125I-Ang II (125I-Ang II) binding (Bmax) was increased in LP rats (control n = 9, 291.6 +/- 27.4 versus LP n = 7, 445.7 +/- 27.4 fmol (mg glomerular protein)(-1), P < 0.01), but affinity (KD) was not statistically different from controls (control 2.87 +/- 0.85 versus LP 0.84 +/- 0.20 pmol 125I-Ang II, P = 0.059). Renal renin activity, tissue Ang II and plasma aldosterone concentrations did not differ between control and LP rats. Increased AT1 receptor expression in LP rat kidneys is consistent with greater haemodynamic sensitivity to Ang II in vivo. This may result in an inappropriate reduction in glomerular filtration rate, salt and water retention, and an increase in blood pressure.
Sahajpal
Vandana
V
Faculty of Life Sciences, University of Manchester, G.38 Stopford Building, Oxford Road, Manchester M13 9PT, UK.
Ashton
Nick
N
D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D018753:Diet, Protein-Restricted / Q000379:methods*; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D007668:Kidney / Q000196:embryology* / Q000378:metabolism*; D008297:Male; D018811:Maternal Exposure; D008431:Maternal-Fetal Exchange / Q000502:physiology; D011247:Pregnancy; D011270:Pregnancy, Animal; D011485:Protein Binding; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism*; D044139:Receptor, Angiotensin, Type 2 / Q000378:metabolism*
D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D000804:Angiotensin II