Physiology and physiopathology of the glomerular function: 'in vivo' studies (glomerular hemodynamic) and 'in vitro' (isolated glomerulus and mesangial cell)

• Grant number: 91/03341-2
• Support Opportunities: Research Projects - Thematic Grants
• Start date: June 01, 1992
• End date: December 31, 1996
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Nestor Schor
• Grantee: Nestor Schor
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Considering the need for us to use multiple experimental protocols so as to better study the manifestations of the glomerular function, we focused this thematic project on 4 groups of experiments, namely: a) protocols 1 to 4: this group intends to focus principally on the hormonal actions and their functional impact on the glomerular function. There have been several vasoactive mediators and cell functions described in this last decade. Their interrelations are complex, making it necessary to study the largest number of hormones possible in different situations; b) protocols 5 and 6: this group has studied several nephrotoxic models, with the majority of them having shown that glomerular alteration occurs through mediators and not as an effect of the toxic agent directly on the glomerular structure. So, using protocols with drugs which modify glomerular filtration, it is intended not only to evaluate the hemodynamic mechanisms involved, but also to inter-relate them with hormonal factors, in the search for a physiopatholgical link with the group of protocols previously mentioned (protocols 1 to 4); c) protocols 7 to 13: the progression of renal disease has been a subject of priority study in the area of nephrology. The glomerular implications as such and the tubulo-intestinal implications leading to a functional deterioration of the kidney are multiple. Hemodynamic modifications, hormonal, metabolic and immunological factors, are some of the mechanisms implicated in the alteration of the glomerular function with the progressive loss of renal function. Thus, in this set of experiments, we intend to evaluate the hormonal effects and the adaptation of the renal microcirculation to varied stimuli (protocols 7,8,9), to the influence in the modification of immunomediated effectors (protocols 10 and 11), to the tubulo-interstitial modification (protocol 12) and the possible alterations in the glomerular hemodynamic in experimental transplant (protocol 13), in the expectation that in these different experimental models we can find a final link in this complex cycle which determines chronic renal insufficiency; d) protocols 14 a 18: in this set of experiments, the final objective will be to focus on the glomerular manifestation in various physiological and physiopathological situations through "in vitro” techniques, using isolated glomeruli and mesangial cells in culture. It is intended to evaluate morphological and functional aspects in given physiological situations (protocol 14 and 15), hormonal stimuli (protocol 16), in nephrotoxic situations (protocol 17) and in chronic renal insufficiency (protocol 18). This set of experiments correlated with the studies carried out "in vivo” by the micropunction technique, will surely provide data for a better understanding of the glomerular function. In this way, it should be emphasized that these experimental protocols, although apparently disparate, are all part of a set encompassing a single objective, that is, to better understand the mechanisms of function, regulation and reaction to different situations of the glomerulus. (AU)