Receptor-Induced Dilatation in the Systemic and Intrarenal Adaptation to Pregnancy in Rats

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.

The renal circulation in normal pregnancy and preeclampsia: is there a place for relaxin?

“…Whether vasodilatory PG play a role is disputed (33,67,94,175), although NO is likely to contribute (3,175). Renal mesangial cells prepared from gravid rats demonstrated an attenuated rise in intracellular calcium in response to AII (72). A comparable attenuation of increases in cytosolic calcium by AII was observed in mesangial cells prepared from nonpregnant rats and incubated with RLN for 24 h (22).…”

International Union of Basic and Clinical Pharmacology. XCV. Recent Advances in the Understanding of the Pharmacology and Biological Roles of Relaxin Family Peptide Receptors 1–4, the Receptors for Relaxin Family Peptides

“…It is interesting to note that the expression of relaxin-RXFP1 as measured by immunohistochemistry and expression of the renin-angiotensin-aldosterone system may both be increased during pregnancy (Ferreira et al, 2009;Cheung and Lafayette, 2013), suggesting another state where RXFP1-AT 2 R heterodimers may have a functional role. However, a study in rat primary mesangial cells did not corroborate this suggestion (Carvalho et al, 2012).…”

Interaction between angiotensin II and relaxin 2 in the progress of growth and spread of prostate cancer cells

“…Interactions between RAS and the relaxin family peptide system have been reported in organ fibrosis (9), blood pressure, in the cardiovascular system (10,11), and osmoregulation, for the central nervous system (12,13) but so far, never in the carcinogenesis of reproductive tissues. However, this study is the first to present the influence of the combined action of angiotensin II and relaxin 2 on various aspects of prostate cancer development and progression.…”