Increased tubuloglomerular feedback activity in Milan hypertensive rats
Boberg, U.; Persson, A.E.
American Journal of Physiology 250(6 Pt 2): F967-F974
1986
ISSN/ISBN: 0002-9513 PMID: 3717352 Document Number: 270346
Studies of whole-kidney function and micropuncture measurements in superficial nephrons were performed to investigate the role of the tubuloglomerular feedback (TGF) in the excretion of salt and water in hydropenic and volume-expanded rats of the spontaneously hypertensive Milan strain (MHS). The rats were 3.5-5 and 5-7 wk old, and age-matched animals from the Milan normotensive strain (MNS) served as controls. There was no difference in mean arterial blood pressure (Pa) between the 3.5- to 5-wk-old prehypertensive MHS (MHSp) and MNS rats, but the glomerular filtration rate (GFR) was higher in MHSp than in MNS [1.35 vs. 0.80 ml .cntdot. min-1 .cntdot. g kidney wt (KW)-1, P < 0.01]. The distal single-nephron glomerular filtration rate (SNGFR) was also higher in MHSp than in MNS (28.6 vs. 20.2 nl .cntdot. min-1 .cntdot. g KW-1, P < 0.05). TGF was determined from both stop-flow pressure response and proximal and distal SNGFR. It was found that MHSp exhibited essentially no TGS response. During development of hypertension 5- to 7-wk-old MHS (MHSd) had a higher Pa than MNS (120 vs. 98 mmHg, P < 0.01). Normally GFR and SNGFR increase with age, and such was the case with MNS (0.8 to 1.02 ml .cntdot. min-1 .cntdot. g KW-1) and 20.2 to 23.4 nl .cntdot. min-1 .cntdot. g (KW-1), but in MHSd there was a decrease in both GFR and SNGFR with age (1.35 to 1.10 ml .cntdot. min-1 .cntdot. g KW-1 and 28.3 to 18.3 nl .cntdot. min-1 .cntdot. g KW-1). The stop-flow feedback sensitivity was significantly higher in MHSd than in MHSp and MNS. In addition, TGF was more activated to reduce SNGFR in MHSd than in MNS, as indicated by a larger difference between proximal and distal SNGFR (38.6 vs. 18.7% of the proximal SNGFR). The very high stop-flow feedback sensitivity in MHSd persisted even after volume expansion. These results indicate that in MHSp there is essentially no TGF activity but that during development of hypertension the TGF system is highly activated to reduce both SNGFR and GFR.