RENAL RESPONSE TO VOLUME DEPLETION AND EXPANSION IN MILAN HYPERTENSIVE RATS

In previous studies on Milan hypertensive (MHS) rats, we found an impaired tubuloglomerular feedback (TGF) response before, during and after development of hypertension. In the present study MHS rats and rats of the Milan normotensive strain (MNS) were investigated after 24 hours of volume depletion (VD) and subsequently after 5% isotonic volume expansion (VE) with respect to whole kidney function, interstitial hydrostatic (P(int)) and oncotic (PI(int)) pressures, stop-flow pressure characteristics of TGF and changes in early proximal flow rate in response to increased loop of Henle flow. MHS rats had higher mean arterial blood pressure (P(a)) than MNS rats (129 vs. 101 mmHg) both after VD and after subsequent VE. No difference in glomerular filtration rate (GFR) was found. Both strains had a low urine flow rate (almost-equal-to 1.5-mu-l min-1) during VD, which increased fourfold after VE. The interstitium was significantly more dehydrated in MHS, as indicated by a more negative net interstitial pressure (P(int)-PI(int)) than in MNS (- 1.3 +/- 0.3 vs. +/- 0.0 +/- 0. 5 mmHg) after VE. The TGF mechanism was more activated in MHS during volume depletion, as indicated by a larger drop in stop-flow pressure (P(sf)) in response to loop of Henle perfusion (7.1 +/- 0.7 vs. 4.7 +/- 0.2 mmHg, P < 0.05). However, during VD the loop of Henle flow that elicited half maximal response in P(sf), the turning point (TP), was equally low in MHS and MNS (I 3.5 +/- 0.6 and 14.3 +/- 0.4, respectively). After VE, however, TP increased significantly more in MNS to (32.6 +/- 2.1 nl min-1) then in MHS (to 21.8 +/- 0.9 nl min-1, P < 0.05). It is concluded that the blunting of the TGF resetting in response to VE in MHS rats may well be of importance in the development of hypertension in the MHS strain.