K. Uzuner et Ro. Banks, ENDOTHELIN-INDUCED NATRIURESIS AND DIURESIS ARE PRESSURE-DEPENDENT EVENTS IN THE RAT, The American journal of physiology, 265(1), 1993, pp. 180000090-180000096
The goal of the current study was to determine the mechanism by which
doses of endothelin (ET) that do not markedly affect the glomerular fi
ltration rate (GFR) cause a natriuresis and diuresis. ET was infused i
nto pentobarbital-anesthetized female rats at 50 ng.kg-1.min-1 iv for
30 min. In controls (n = 6 rats; n = 5 in all other groups), ET increa
sed mean arterial blood pressure (MAP) from 95 +/- 2 to 131 +/- 2 (SE)
mmHg, Na excretion (U(Na)V) from 0.34 +/- 0.07 to 1.83 +/- 0.2 meq/mi
n, and urine flow rate (V) from 13 +/- 1 to 24 +/- 3 ml/min (all P < 0
.01 vs. baseline). At 15 min during infusion of ET, the GFR was not af
fected (2.1 +/- 0.1 to 2.2 +/- 0.1 ml/min) but modestly decreased to 1
.8 +/- 0.1 ml/min at 30 min (P < 0.05 vs. baseline). Either removing t
he capsule from both kidneys during surgery or maintaining renal arter
ial pressure at baseline values with an adjustable clamp on the aorta
above the right renal artery abolished the ET-induced increase in U(Na
)V and V. Meclofenamate also did not alter the ET-induced increase in
MAP, V, or U(Na)V. To determine the intrarenal site of action of ET, e
xperiments were conducted with ET plus amiloride or with a combination
of amiloride plus furosemide; there was a larger ET-induced diuresis
and natriuresis in amiloride-treated rats and an even larger response
with amiloride plus furosemide compared with controls. Finally, as a c
ontrol for the decapsulation procedure, amiloride alone resulted in si
milar increases in V and U(Na)V in intact rats as in rats without rena
l capsules. Our data indicate that ET-induced natriuresis and diuresis
are arterial blood pressure-related phenomena (pressure natriuresis a
nd diuresis) resulting from an inhibition of sodium reabsorption proxi
mal to the thick ascending limb and that changes in prostaglandin synt
hesis are not involved.