Abstract
Normal pregnancy is associated with systemic and intrarenal vasodilatation resulting in an increased glomerular filtration rate. This adaptive response occurs in spite of elevated circulating levels of angiotensin II (Ang II). In the present study, we evaluated the potential mechanisms responsible for this adaptation. The reactivity of the mesangial cells (MCs) cultured from 14-day-pregnant rats to Ang II was measured through changes in the intracellular calcium concentration ([Cai]). The expression levels of inducible nitric oxide synthase (iNOS), the Ang II-induced vasodilatation receptor AT2, and the relaxin (LGR7) receptor were evaluated in cultured MCs and in the aorta, renal artery and kidney cortex by real time-PCR. The intrarenal distribution of LGR7 was further analyzed by immunohistochemistry. The MCs displayed a relative insensitivity to Ang II, which was paralleled by an impressive increase in the expression level of iNOS, AT2 and LGR7. These results suggest that the MCs also adapt to the pregnancy, thereby contributing to the maintenance of the glomerular surface area even in the presence of high levels of Ang II. The mRNA expression levels of AT2 and LGR7 also increased in the aorta, renal artery and kidney of the pregnant animals, whereas the expression of the AT1 did not significantly change. This further suggests a role of these vasodilatation-induced receptors in the systemic and intrarenal adaptation during pregnancy. LGR7 was localized in the glomeruli and on the apical membrane of the tubular cells, with stronger labeling in the kidneys of pregnant rats. These results suggest a role of iNOS, AT2, and LGR7 in the systemic vasodilatation and intrarenal adaptation to pregnancy and also suggest a pivotal role for relaxin in the tubular function during gestation.
Highlights
The maternal adaptation to pregnancy includes a reduced vascular reaction to vasoconstrictors, which results in systemic and intrarenal vasodilatation followed by increases in the renal plasma flow and the glomerular filtration rate [1,2]
The expression of the target mRNA was normalized to the mRNA expression of b-actin for each sample, and the results are expressed as a relative ratio compared to the average of the normal group
The mRNA expression level of all molecules except AT1 was significantly elevated in mesangial cells (MCs) from the pregnant group, especially the inducible nitric oxide synthase (iNOS) mRNA expression level, which was 28-fold higher than the virgin group
Summary
The maternal adaptation to pregnancy includes a reduced vascular reaction to vasoconstrictors, which results in systemic and intrarenal vasodilatation followed by increases in the renal plasma flow and the glomerular filtration rate [1,2]. The chronic administration of relaxin to nonpregnant female and male rats resulted in hyperfiltration [11,12] and decreased myogenic reactivity of the small renal arteries [13], similar to the changes observed during pregnancy. The main relaxin receptor, a leucine-rich repeat G-protein coupled receptor designated LGR7 or RXFP1 [17], is expressed in the aorta and small renal and mesenteric arteries in nonpregnant female and male rats [18]. This suggests a role of LGR7 in arterial function independently of pregnancy. To our knowledge, there are no data on the arterial or intrarenal expression level of LGR7 during pregnancy
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