Tubuloglomerular feedback in hypertensive rats of the Milan strain

Abstract

In rats of the Milan hypertensive strain (MHS) the disease can be transplanted with the kidney to rats of the Milan normotensive strain (MNS). GFR [glomerular filtration rate] salt and volume regulation differ between MHS and MNS rats. Tubuloglomerular feedback control mechanism (TGF) is important for body volume regulation, the TGF control in MHS and MNS rat was studied. Whole kidney and micropuncture experiments were done before and during saline volume expansion (5% of body wt). In an initial series of experiments measurements were made of total kidney GFR, urine excretion rate of Na and K and subcapsular interstitial hydrostatic pressure (.rho.sc); interstitial oncotic pressure (.pi.int) was estimated from hilar lymph protein concentration. In a 2nd series, proximal tubular stop-flow pressure (.rho.sf) was determined upstream from a wax block while the distal nephron was being perfused with Ringer solution at a flow rate varying from 0-40 nl .cntdot. min-1. In this way the maximal drop in stop-flow pressure (.DELTA..rho.pst) and also the turning point (TP), the tubular flow rate at which 50% of this response was achieved, could be determined after saline volume expansion and after 2 h of complete ureteral occlusion. GFR was similar in MHS and MNS rats in the control situation, but that during volume expansion it was significantly lower in the MHS group. Interstitial .rho.sc and nint and net interstitial pressure (.rho.sc.sbd..pi.int) were similar in MHs and MNS rats both under control conditions and during volume expansion. The TGF investigaton showed a slightly increased .DELTA..rho.sf (8.5 vs. 5.2 mm Hg) in the MHS animals while .rho.sf and TP were normal in the control state (38 mm Hg) and 21 nl .cntdot. min-1). During volume expansion, the TGF sensitivity was significantly higher in the MHS animals than in the normotensive controls, showing a TP of 25 nl .cntdot. min-1 (MNs 39 nl .cntdot. min-1) and a .DELTA..rho.sf of 5.6 mm Hg, (MNS 1.3 mm Hg). During ureteral occlusion the resetting to a low TGF sensitivity that occurs in control animals did not take place in the hypertensive animals. The feedback sensitivity was reset to a low level in the MNS animals during volume expansion and ureteral occlusion, while the MHS animals were unable to reset this sensitivity in the normal way. This inability might be expected to lead to overloading of the extracellular fluid volume, which may particpate in the development and maintenance of the hypertensive disease.