The kidney responds to high levels of ANG II, as may occur during
malignant hypertension, by increasing
sodium and water excretion. To study whether kidney medullary transporters contribute to this response, rats were made hypertensive using ANG II. Within 3 days of being given ANG II, systolic blood pressure (BP) was increased (200 mmHg), vs control (130 mmHg), and remained high through day 14. Kidney inner medullary (IM) tip and base and outer medulla were analyzed for transporter
protein abundance. There were significant decreases in UT-A1
urea transporter,
aquaporin-2 (AQP2)
water channel, and NKCC2/BSC1 Na(+)-K(+)-2Cl(-) cotransporter. To determine whether the decreases were a response to
hypertension, ANG II, or an ANG II-induced increase in
aldosterone, rats were given 1)
norepinephrine (to increase BP) and 2) ANG II plus
spironolactone (to block the
mineralocorticoid receptor).
Norepinephrine (7 days) increased BP, urine volume,
sodium excretion, and decreased urine osmolality and UT-A1, AQP2, and NKCC2/BSC1 abundances, similar to ANG II. ANG II alone or with
spironolactone yielded similar increases in BP, urine volume, and urine osmolality, and decreases in UT-A1 and AQP2
proteins in the IM tip. Plasma
vasopressin was unaffected by treatment. Water diuresis did not change UT-A1 but decreased AQP2 and NKCC2/BSC1 abundances. We conclude that decreases in UT-A1, AQP2, and NKCC2/BSC1
proteins may contribute to the diuresis and natriuresis that occur following ANG II or
norepinephrine-induced acute
hypertension and do not appear to involve ANG II stimulation of
aldosterone or thirst.