Exaggerated tubuloglomerular feedback activity in spontaneously
hypertensive rats mediated by angiotensin ii and at1 receptors.
Br[umlaut]annstr[diaeresis]om, Kristina, Peter Morsing, and William J.
Arendshorst.
Department of Physiology, University of North Carolina at Chapel
Hill
APStracts 2:0199F, 1995.
The purpose of the present study was to determine the role of
endogenous angiotensin II in exaggerated tubuloglomerular feedback
(TGF) observed in young, euvolemic SHR. TGF was characterized by
measuring proximal tubular stop-flow pressure (Psf) responses to loop
of Henle perfusion before and during losartan infusion in 7-week old
SHR and WKY. In the control period, TGF responses were exaggerated in
SHR compared to WKY. This was evidenced by a larger flow-induced
maximum decrease in Psf (19 vs. 13 mmHg), lower turning point (8 vs.
12 nl/min) and higher reactivity (-6.4 vs. -3.0 mmHg/nl/min) in SHR.
Losartan (DuP 753) was infused into the renal artery to antagonize
angiotensin AT1 receptors in the experimental period. This was
verified by losartan inhibiting more than 90 % of the decrease in
whole kidney and superficial cortical blood flow produced by
exogenous angiotensin II in both strains. Losartan infusion
significantly attenuated TGF activity in SHR but not in WKY. In SHR
losartan reduced the maximum Psf response (19 to 10 mmHg) and
increased the turning point (8 to 11 nl/min). SHR values during
losartan administration were similar to those obtained in WKY. WKY
values were unaffected by losartan. The lack of change in maximum TGF
responses after losartan treatment was not unique to WKY, as similar
results were obtained in euvolemic Munich-Wistar rats (- 2.0 +/- 0.7
and - 1.1 +/- 1.0 mmHg vs. - 8.4 +/- 0.7 mmHg in SHR). Thus,
angiotensin II does not appear to play an essential role in basal TGF
activity during euvolemia in normotensive animals when there is
minimal stimulation of the renin-angiotensin system. In contrast, our
observations indicate that the exaggerated TGF in young euvolemic SHR
represents a functional resetting that is dependent on angiotensin II
and losartan-sensitive AT1 receptors during the development of
genetic hypertension.
Received 8 June 1995; accepted in final form 27 October 1995.
APS Manuscript Number F187-5.
Article publication pending Am. J. Physiol. (Renal Fluid Electrolyte
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 30 November 95