Elevated arterial pressure impairs autoregulation independently of AT 1 receptor activation

Academic Article


  • Objective: These studies determined the ability of AT1 receptor blockade or 'triple therapy', to reverse angiotensin II-induced hypertension and improve autoregulatory behavior. Design: Experiments to determine if regulation of systolic blood pressure, in the normotensive range, would improve renal microvascular autoregulatory behavior in angiotensin II-infused rats. Methods: Hypertension was induced by chronic angiotensin II infusion (60 ng/min) for 10-14 days. Two groups of angiotensin II-infused rats received either AT 1 receptor blockade, with candesartan cilexetil, or triple therapy, with hydralazine, hydrochlorothiazide and reserpine, beginning on day 6 or day 0 of angiotensin II infusion, respectively. Sham animals were studied as normotensive controls. Systolic blood pressure was measured by tail cuff. Autoregulatory behavior was assessed using the juxtamedullary nephron technique in response to step (15 mmHg) increases in perfusion pressure from 65 to 170 mmHg. Results: Angiotensin II infusion increased systolic blood pressure from a baseline of 125 mmHg to 162 and 182 mmHg after 10 and 14 days, respectively. Candesartan cilexetil and triple therapy normalized the blood pressure to between 119 and 126 mmHg. Increasing perfusion pressure, from 65 to 170 mmHg, reduced afferent arteriolar diameter by 30% in sham-treated kidneys. Autoregulation was significantly blunted in angiotensin II-infused rats, resulting in a pressure-mediated vasoconstriction of only 10%. Candesartan cilexetil, or triple therapy, significantly improved autoregulatory behavior, as indicated by pressure-mediated vasoconstrictor responses of 30 and 40%; respectively, despite continued angiotensin II infusion. Conclusions: These data suggest that chronic elevation of arterial blood pressure, rather than chronic AT1 receptor stimulation, is sufficient to induce hypertensive impairment of renal autoregulatory capability. © 2004 Lippincott Williams & Wilkins.
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    Digital Object Identifier (doi)

    Author List

  • Inscho EW; Cook AK; Murzynowski JB; Imig JD
  • Start Page

  • 811
  • End Page

  • 818
  • Volume

  • 22
  • Issue

  • 4