The blunted response to angiotensin II (Ang II) during pregnancy is lost in patients by preeclampsia. This impaired response has been attributed to a change in one or both of the Ang II receptors, type 1 (AT(1)R) and type 2 (AT(2)R). The ratio of the Ang II receptor types in the kidney has not been studied. We postulated that an imbalance exists between AT(1)R/AT(2)R receptors in the renal cortex from rats subjected to an experimental model of preeclampsia, and that this altered ratio can modify the characteristic blunted pressor response to Ang II during pregnancy. The feto-placental units of Wistar rats were made ischemic by subrenal aortic coarctation, thus creating an experimental model of preeclampsia. We measured the AT(1)R and AT(2)R protein expression and the presence of the heterodimer AT(1)R/AT(2)R in the renal cortex and evaluated the pressor response to Ang II in an isolated kidney preparation from non-pregnant, healthy pregnant, and preeclampsia model rats. Pregnancy increased AT(2)R and AT(1)R/AT(2)R heterodimer expression and decreased the pressor response to Ang II. In contrast, AT(1)R increased, while AT(2)R and AT(1)R/AT(2)R heterodimer decreased in the preeclampsia model group. Thus, Ang II hypersensitivity observed in preeclampsia might be related to an increased expression of AT(1)R over AT(2)R and to a decreased presence of the AT(1)R/AT(2)R heterodimer in renal cortex.
Pregnancy courses with low response to angiotensin II and adrenergic agonists. In preeclampsia, both effects are reverted. It is known that angiotensin II regulates adrenergic system. It is not known, however, the interaction between both systems receptors. Our aim was to study if AT(1)R and alpha1D adrenoceptor heterodimerize in preeclampsia. We used subrenal aorctic coarctation in pregnant rats. Aortic tissues were prepared for confocal imaging and coimmunoprecipitated for alpha1D and AT(1) receptors. We found that AT(1)R and alpha1D adrenoceptor heterodimerize in both, healthy and preeclamptic groups. In healthy pregnant rats, heterodimer is barely detected. In preeclamptic rats however, we found higher heterodimerization. These results suggest that AT(1)R and alpha1D -adrenoceptor may form heterodimers, and may play a role in preeclampsia.
Background:
Liver ailments are among the leading causes of death; they originate from viral
infections, chronic alcoholism, and autoimmune illnesses, which may chronically be precursors of
cirrhosis; furthermore, metabolic syndrome may worsen those hepatopathies or cause Non-alcoholic
Fatty Liver Disease (NAFLD) that may advance to non-alcoholic steatohepatitis (NASH). Cirrhosis is
the late-stage liver disease and can proceed to hepatocellular carcinoma (HCC). Pharmacological
treatment options for liver diseases, cirrhosis, and HCC, are limited, expensive, and not wholly effective.
The use of medicinal herbs and functional foods is growing around the world as natural resources
of bioactive compounds that would set the basis for the development of new drugs.
Review and Conclusion:
Plant and food-derived sterols and triterpenoids (TTP) possess antioxidant,
metabolic-regulating, immunomodulatory, and anti-inflammatory activities, as well as they are recognized
as anticancer agents, suggesting their application strongly as an alternative therapy in some
chronic diseases. Thus, it is interesting to review current reports about them as hepatoprotective agents,
but also because they structurally resemble cholesterol, sexual hormones, corticosteroids and bile acids
due to the presence of the steroid nucleus, so they all can share pharmacological properties through activating
nuclear and membrane receptors. Therefore, sterols and TTP appear as a feasible option for the
prevention and treatment of chronic metabolic-related liver diseases, cirrhosis, and HCC.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.