Cft. Uyehara et M. Gellai, IMPAIRMENT OF RENAL-FUNCTION PRECEDES ESTABLISHMENT OF HYPERTENSION IN SPONTANEOUSLY HYPERTENSIVE RATS, The American journal of physiology, 265(4), 1993, pp. 180000943-180000950
To determine renal function throughout development of hypertension in
the spontaneously hypertensive rat (SHR) and its normotensive counterp
art, the Wistar-Kyoto rat (WKY), renal clearance studies were performe
d at 2-wk intervals from 4 to 12 wk and again at 16 wk of age in consc
ious chronically instrumented rats after recovery (4-6 days) from surg
ery. The data indicate that the critical period for the development of
hypertension in SHR was between 4 and 6 wk of age. Mean arterial pres
sure sharply increased from 107 +/- 5 (n = 6) to 145 +/- 6 mmHg (n = 6
) between 4 and 6 wk of age, did not change between 6 and 10 wk of age
, and gradually rose between 10 and 16 wk of age to 183 +/- 3 mmHg. In
WKYs, blood pressure increased only slightly from 97 +/- 3 mmHg at 4
wk of age (n = 8) to 110 +/- 3 mmHg at 8 wk of age (n = 8), where it r
emained through adulthood. Glomerular filtration rate (GFR) in the 4-w
k-old SHR was significantly decreased compared with WKY (0.94 +/- 0.03
vs. 1.11 +/- 0.04 ml.min-1.g wet kidney wt-1), and it recovered to no
rmal level and stabilized by 6 wk of age (1.14 +/- 0.04 ml.min-1.g wet
kidney wt-1). Renal blood flow was lower in the SHR only at 4 and 16
wk; it increased with age in both groups. Renal vascular resistance wa
s higher in the SHR at 4 wk and remained elevated throughout the obser
vation period. Clearance of osmoles was decreased in the 4-wk-old SHR
and increased at 6 wk of age parallel with the increases in mean arter
ial pressure and GFR. GFR and clearance of osmoles were the same in th
e WKY at all ages. These results demonstrate that in SHR renal functio
n is impaired before the establishment of sustained hypertension; they
are consistent with the hypothesis that blood pressure increases to c
ompensate for impaired renal function in genetic hypertension.