Circadian rhythm of the intrarenal renin–angiotensin system is caused by glomerular filtration of liver-derived angiotensinogen depending on glomerular capillary pressure in adriamycin nephropathy rats

Background. The purpose of the study was to explore the role of the renin-angiotensin system in the disturbance of renal excretory function in the dynamics of alloxan-induced experimental diabetes mellitus. Materials and methods. The experiments were carried out on 78 white non-linear mature male rats with 11-, 26- and 46-day long experimental diabetes mellitus caused by intraperitoneal administration of alloxan (160 mg/kg), against the background of pharmacological blockade of intrarenal renin-angiotensin system, induced by intraperitoneal administration of сaptopril (10 mg/kg). The study of excretory function of the kidneys was provided by the clearance method under the condition of induced water 2-hour diuresis to determine the clearance of endogenous creatinine, glomerular filtration rate, relative water reabsorption, protein content in urine, its excretion. Results. Analysis of changes in renal function after pharmacological blockade of the renin-angiotensin system in rats on day 11 of alloxan diabetes showed a significant increase in diuresis, glomerular filtration rate, endogenous creatinine concentration index, and protein excretion. The pharmacological blockade of the renin-angiotensin system had practically no effect on the intensity of the relative reabsorption of water in alloxan-diabetic rats. On day 26 of alloxan diabetes after captopril administration, there was a slight decrease in final urine volume, glomerular filtration rate, relative water reabsorption, and endogenous creatinine concentration index. At the same time, captopril did not cause an antiproteinuric effect, and protein excretion even demonstrated a tendency to increase. On day 46 of alloxan-induced diabetes after administration of captopril, there was a significant reduction in diuresis, endogenous creatinine clearance and glomerular filtration rate of rats, as well as in urinary protein concentration and excretion. Conclusions. The results of the study allow us to conclude that the initial stage of renal disorders formation in alloxan-induced experimental diabetes is associated with hemodynamic-hyperperfusion nature of renal functioning with preserved renal functional reserve and the structure of the glomerular-tubular apparatus of the kidney, autoregulatory mechanisms. Mentioned compensatory-functional changes in renal function are gradually complicated by an exhaustion of renal functional reserve and pathological activation of intrarenal renin-angiotensin system with subsequent progression of hyperperfusion-ischemic kidney damage, a decrease in the number of functioning nephrons.

Download Full-text

Role of the Renin-Angiotensin System in the Regulation of Glomerular Filtration

Journal of Cardiovascular Pharmacology ◽

10.1097/00005344-198900000-00006 ◽

1989 ◽

Vol 14 (4) ◽

pp. S21-S25 ◽

Cited By ~ 7

Author(s):

J. D. Sraer ◽

A. Kanfer ◽

E. Rondeau ◽

R. Lacave

Keyword(s):

Glomerular Filtration ◽

Renin Angiotensin System ◽

Angiotensin System ◽

Renin Angiotensin

Download Full-text

Impaired renal hemodynamics and glomerular hyperfiltration contribute to hypertension-induced renal injury

AJP Renal Physiology ◽

10.1152/ajprenal.00239.2020 ◽

2020 ◽

Vol 319 (4) ◽

pp. F624-F635 ◽

Cited By ~ 2

Author(s):

Letao Fan ◽

Wenjun Gao ◽

Bond V. Nguyen ◽

Joshua R. Jefferson ◽

Yedan Liu ◽

...

Keyword(s):

Glomerular Filtration Rate ◽

Glomerular Filtration ◽

Capillary Pressure ◽

Renal Injury ◽

Filtration Rate ◽

Time Course ◽

Renal Hemodynamics ◽

Myogenic Response ◽

Glomerular Capillary ◽

Glomerular Capillary Pressure

Recently, we reported a mutation in γ-adducin (ADD3) was associated with an impaired myogenic response of the afferent arteriole and hypertension-induced chronic kidney disease (CKD) in fawn hooded hypertensive (FHH) rats. However, the mechanisms by which altered renal blood flow (RBF) autoregulation promotes hypertension-induced renal injury remain to be determined. The present study compared the time course of changes in renal hemodynamics and the progression of CKD during the development of DOCA-salt hypertension in FHH 1BN congenic rats [wild-type (WT)] with an intact myogenic response versus FHH 1BN Add3KO ( Add3KO) rats, which have impaired myogenic response. RBF was well autoregulated in WT rats but not in Add3KO rats. Glomerular capillary pressure rose by 6 versus 14 mmHg in WT versus Add3KO rats when blood pressure increased from 100 to 150 mmHg. After 1 wk of hypertension, glomerular filtration rate increased by 38% and glomerular nephrin expression decreased by 20% in Add3KO rats. Neither were altered in WT rats. Proteinuria doubled in WT rats versus a sixfold increase in Add3KO rats. The degree of renal injury was greater in Add3KO than WT rats after 3 wk of hypertension. RBF, glomerular filtration rate, and glomerular capillary pressure were lower by 20%, 28%, and 19% in Add3KO rats than in WT rats, which was associated with glomerular matrix expansion and loss of capillary filtration area. The results indicated that impaired RBF autoregulation and eutrophic remodeling of preglomerular arterioles increase the transmission of pressure to glomeruli, which induces podocyte loss and accelerates the progression of CKD in hypertensive Add3KO rats.

Download Full-text

Effect of feeding on glomerular filtration rate and proteinuria in conscious aging rats

AJP Renal Physiology ◽

10.1152/ajprenal.1988.255.2.f250 ◽

1988 ◽

Vol 255 (2) ◽

pp. F250-F256 ◽

Cited By ~ 3

Author(s):

B. Corman ◽

S. Chami-Khazraji ◽

J. Schaeverbeke ◽

J. B. Michel

Keyword(s):

Glomerular Filtration Rate ◽

Food Intake ◽

Glomerular Filtration ◽

Filtration Rate ◽

Renin Angiotensin System ◽

Experimental Conditions ◽

Angiotensin System ◽

System Activity ◽

Renin Angiotensin ◽

Old Rats

Food intake increases glomerular filtration and proteinuria in adult rats. That this postprandial hyperfiltration could be age dependent was investigated in 3-, 10-, 20-, and 30-mo-old rats. Glomerular filtration rate and protein excretion were measured in fed or 24 h fasted conscious animals. In the 3-mo-old rats food ingestion increased renal filtration by 45% from 1.17 +/- 0.08 to 1.73 +/- 0.11 ml.min-1.g kidney wt-1 (n = 6). As the animals became older, the differences between fed and fasted periods became smaller: in 30-mo-old rats glomerular filtration rate was 0.85 +/- 0.03 and 1.01 +/- 0.06 ml.min-1.g kidney wt-1 (n = 6) in fasted and fed conditions, respectively. Proteinuria, which was mainly albuminuria, increased slightly with age and was more markedly reduced by acute food restriction in the 30-mo-old than in the 3-mo-old rats. Because the renin-angiotensin system activity decreases with age, its role in postprandial hyperfiltration was assessed by measuring glomerular filtration in 3-mo-old animals whose angiotensin II converting-enzyme activity was chronically inhibited by daily administration of perindopril. In such experimental conditions there was no longer a difference in renal filtration between fed and fasted rats. These data indicate that 1) postprandial increase in glomerular filtration is to some extent related to the renin-angiotensin system activity; 2) short-term reduction of food intake reduces proteinuria even in senescent rats, although the feeding dependence of the glomerular filtration is blunted with age.

Download Full-text