Autoregulation of renal blood flow and pressure-dependent renin release in autosomal dominant polycystic kidney disease of rats.
The Han:SPRD (PKD) rat is a new animal model of autosomal dominant polycystic kidney disease (ADPKD) which resembles many clinical and pathoanatomical features of human ADPKD. The aim of the present study was to analyse age-dependent changes in renal haemodynamics and renal renin secretion which could be of pathophysiological importance in the course of the disease. We investigated glomerular filtration rate (GFR), renal blood flow (RBF), renal vascular resistance (RVR), plasma renin activity (PRA), the autoregulatory behaviour of RBF and the pressure-dependent plasma renin activity in conscious PKD rats compared with age-matched controls. Experiments were performed in conscious chronically instrumented PKD rats (age: 3 and 9 months) and their age-matched genetic controls. GFR in 3-(0.52 +/- 0.07 ml/min/100 g; n = 9) and 9-month-old (0.42 +/- 0.03 ml/min/100 g; n = 21) PKD rats were significantly lower (P < 0.05) than 3- (0.92 +/- 0.07 ml/min/100 g; n = 17) and 9-month-old (0.67 +/- 0.05 ml/min/100 g; n = 17) controls. Nine-month-old PKD revealed a significant (P < 0.005) resetting of the breakpoint of RBF autoregulation towards lower pressures (85.5 +/- 4.4 mmHg; n = 10) than either age-matched controls (102.8 +/- 2.5 mmHg; n = 11) or young PKD (107.5 +/- 4.4 mmHg; n = 6). The basal plasma renin activity was significantly (P < 0.05) lower in 3-month-old PKD than in old PKD and age-matched controls. A significant shift of threshold pressure for pressure-dependent renin release to lower pressures was observed in PKD rats. The observed improvement of autoregulatory reserve, at least in the low pressure range, could be of pathophysiological importance in delaying the progression of chronic renal failure in ADPKD. The suppression of the renin angiotensin system in young PKD could explain the fact that we did not observe hypertension in PKD rats, which is a major difference between this animal model and human ADPKD.
Braun
C
C
V. Medical Department, University of Heidelberg, Klinikum, Mannheim, Germany.
Lüdicke
C
C
Rebsch
W
W
Gretz
N
N
van der Woude
F J
FJ
Rohmeiss
P
P
D000375:Aging / Q000502:physiology; D000818:Animals; D001794:Blood Pressure / Q000502:physiology*; D006706:Homeostasis; D008297:Male; D016891:Polycystic Kidney, Autosomal Dominant / Q000097:blood / Q000503:physiopathology / Q000662:veterinary*; D051381:Rats / Q000378:metabolism; D011922:Rats, Mutant Strains; D012079:Renal Circulation; D012083:Renin / Q000097:blood*; D012376:Rodent Diseases / Q000097:blood* / Q000503:physiopathology*
D012083:Renin