Urea transporter UT-A1 and aquaporin-2 proteins decrease in response to angiotensin II or norepinephrine-induced acute hypertension.

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.
AuthorsJanet D Klein, Brian P Murrell, Suzanne Tucker, Young-Hee Kim, Jeff M Sands
JournalAmerican journal of physiology. Renal physiology (Am J Physiol Renal Physiol) Vol. 291 Issue 5 Pg. F952-9 (Nov 2006) ISSN: 1931-857X [Print] United States
PMID16788141 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Chemical References
  • Aqp2 protein, rat
  • Aquaporin 2
  • Membrane Transport Proteins
  • Mineralocorticoid Receptor Antagonists
  • Slc12a1 protein, rat
  • Sodium-Potassium-Chloride Symporters
  • Solute Carrier Family 12, Member 1
  • UT-A1 protein, rat
  • Vasoconstrictor Agents
  • Water
  • Angiotensin II
  • Spironolactone
  • Aldosterone
  • Urea
  • Norepinephrine
  • Acute Disease
  • Aldosterone (blood)
  • Angiotensin II (pharmacology)
  • Animals
  • Aquaporin 2 (metabolism)
  • Blood Pressure (drug effects)
  • Drinking (drug effects, physiology)
  • Hypertension, Renal (chemically induced, metabolism)
  • Male
  • Membrane Transport Proteins (metabolism)
  • Mineralocorticoid Receptor Antagonists (pharmacology)
  • Norepinephrine (pharmacology)
  • Rats
  • Rats, Sprague-Dawley
  • Sodium-Potassium-Chloride Symporters (metabolism)
  • Solute Carrier Family 12, Member 1
  • Spironolactone (pharmacology)
  • Thirst (drug effects, physiology)
  • Urea (metabolism)
  • Vasoconstrictor Agents (pharmacology)
  • Water (metabolism)

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