LONG-TERM CONSEQUENCES IN ADULT LIFE OF IMPAIRED RENAL MEDULLARY MICROVASCULAR FORMATION DURING KIDNEY DEVELOPMENT

• Grant number: 19/02490-1
• Support type: Scholarships abroad - Research Internship - Doctorate
• Effective date (Start): May 21, 2019
• Effective date (End): May 20, 2020
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal researcher: Terezila Machado Coimbra
• Grantee: Lucas Ferreira de Almeida
• Supervisor abroad: Kirsten Madsen
• Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Research place: University of Southern Denmark (SDU), Denmark
• Associated to the scholarship: 17/07118-8 - Influence of vitamin D on renal development in rats, BP.DR

Abstract

Adverse events during fetal development are associated with increased risk of hypertension and cardiovascular and metabolic diseases later in life, a correlation know as fetal programing. The kidneys are particularly prone to fetal programming alterations specially when there is a disruption on the renin-angiotensin cascade during development. One of the specific targets of these alterations is the kidney vasculature. An elegant study by professor Madsen's group, using unbiased quantitative stereologic methods demonstrated a reduction in expansion for postglomerular recta bundles in rats during lactation in response to pharmacological AT1 receptor antagonism in the postnatal period. The long-term effects of this receptor blockade are still yet to be investigated. Thus, we propose an elegant collaborative study between the two research groups to explore the long term effects of the pharmacological blockage of AT1. We hypothesized that postnatal development of the kidney depends on AngII-stimulated angiogenesis and that medullary injury after RAS inhibition is caused by impaired development of the microvasculature that persists in adulthood. The hypothesis will be addressed in vivo by application of unbiased quantitative stereologic methods. Postglomerular microvascular length, volume, and surface area will be determined in rat kidneys at P 90 after treatment with AngII type 1 (AT1) inhibitor during the 10-15 days of postnatal life. Mechanisms will be addressed by analysis of novel signaling pathways involved in angiogenesis in the renal medulla during kidney development. The obtained results will make possible the comparison with the Vit.D deficiency results previously obtained in our laboratory.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

ALMEIDA, LUCAS F.; TOFTENG, SIGNE S.; MADSEN, KIRSTEN; JENSEN, BOYE L.. Role of the renin-angiotensin system in kidney development and programming of adult blood pressure. Clinical Science, v. 134, n. 6, p. 641-656, MAR 2020. (19/02490-1)