AT<sub>2</sub> receptors mediate tonic renal medullary vasoconstriction in renovascular hypertension

Duke, Lisa Michelle; Widdop, Robert E; Kett, Michelle M; Evans, Roger G.

doi:10.1038/sj.bjp.0706036

Cited by 26 publications

(27 citation statements)

References 43 publications

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“…Similarly, intravenous infusion of ANG II in rats reduced TRBF and CLDF at doses without effect on MLDF (3,4). In contrast, renal arterial infusion of the V 1 agonist [Phe 2 ,Ile 3 ,Orn 8 ]-vasopressin in rabbits caused selective reductions in MLDF without significant changes in TRBF or CLDF (7,25).…”

Section: Discussionmentioning

confidence: 95%

Renal medullary tissue oxygenation is dependent on both cortical and medullary blood flow

O’Connor¹,

Kett²,

Anderson³

et al. 2006

American Journal of Physiology-Renal Physiology

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. Renal medullary tissue oxygenation is dependent on both cortical and medullary blood flow. Am J Physiol Renal Physiol 290: F688 -F694, 2006. First published October 11, 2005 doi:10.1152/ajprenal.00275.2005The aim of the current study was to determine whether renal medullary oxygenation is independent of the level of cortical blood flow by testing responses to stimuli that selectively reduce blood flow in either the cortex or medulla. In anesthetized rabbits, renal arterial infusion of [Phe 2 ,Ile 3 ,Orn 8 ]-vasopressin selectively reduced medullary perfusion and PO 2 (Ϫ54 Ϯ 24 and Ϫ50 Ϯ 10%, respectively) but did not significantly affect cortical perfusion or tissue oxygenation. In contrast, stimulation of the renal nerves resulted in renal cortical ischemia with reductions in total renal blood flow (Ϫ76 Ϯ 3% at 4 Hz), cortical perfusion (Ϫ57 Ϯ 17%), and cortical PO 2 (Ϫ44 Ϯ 12%). Medullary tissue PO2 was reduced by Ϫ70 Ϯ 5% at 4 Hz, despite medullary perfusion being unaffected and distal tubular sodium reabsorption being reduced (by Ϫ83.3 Ϯ 1.2% from baseline). In anesthetized rats, in which renal perfusion pressure was maintained with an aortic constrictor, intravenous infusion of ANG II (0.5-5 g ⅐ kg Ϫ1 ⅐ min Ϫ1 ) dose dependently reduced cortical perfusion (up to Ϫ65 Ϯ 3%; P Ͻ 0.001) and cortical PO 2 (up to Ϫ57 Ϯ 4%; P Ͻ 0.05). However, medullary perfusion was only significantly reduced at the highest dose (5 g ⅐ kg Ϫ1 ⅐ min Ϫ1 ; by 29 Ϯ 6%). Medullary perfusion was not reduced by 1 g ⅐ kg Ϫ1 ⅐ min Ϫ1ANG II, but medullary PO2 was significantly reduced (Ϫ12 Ϯ 4%). Thus, although cortical and medullary blood flow may be independently regulated, medullary oxygenation may be compromised during moderate to severe cortical ischemia even when medullary blood flow is maintained.acute renal failure; acute tubular necrosis; hypoxia; ischemia; laserDoppler flowmetry; fluorescence oximetry; oxygen; rabbits; rats; renal circulation THE UNIQUE VASCULAR architecture of the kidney allows differential regulation of cortical and medullary blood flow (7,10,14). Indeed, many vasoconstrictor factors that profoundly reduce total renal blood flow (TRBF) and cortical blood flow appear to have considerably less impact on medullary blood flow (6). Thus the renal medulla may be at least partially protected from hypoxic insults during periods of reduced overall (total) renal blood flow, if medullary blood flow, and so presumably oxygen delivery to this region, is maintained. However, this hypothesis is predicated on renal cortical and medullary oxygenation being relatively independent. Changes in glomerular filtration, tubular sodium reabsorption, and/or the possibility of oxygen loss from preglomerular arterial blood (27) may render medullary oxygenation dependent on the level of cortical blood flow.The aim of the current study was to examine the relationship between tissue oxygenation and perfusion in the cortex and medulla. We tested the hypothesis that medullary oxygenation is independent of cortical blood flow. To achieve this...

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Section: Discussionmentioning

confidence: 95%

Renal medullary tissue oxygenation is dependent on both cortical and medullary blood flow

O’Connor¹,

Kett²,

Anderson³

et al. 2006

American Journal of Physiology-Renal Physiology

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“…The RPP was adjusted by constriction of the suprarenal clamp and was monitored by a pressure catheter placed in the femoral artery below the level of the clamp. Ten minutes thereafter, there was a 30-minute clearance period with blood bolus ϩ 1 mg ⅐ kg bw Ϫ1 ⅐ h Ϫ1 , Sigma Aldrich) 26 followed after 30 minutes by enalaprilat (group 7), after candesartan alone (1 mg ⅐ kg bw Ϫ1 bolus ϩ1 mg ⅐ kg bw Ϫ1 ⅐ h Ϫ1 , kind gift from Astra Zeneca, Södertälje, Sweden; manufacturer-recommended dose for maximal inhibition of AT 1 receptors in vivo), followed after 30 minutes by enalaprilat (group 8), or after N G -nitro-L-arginine methyl ester (L-NAME) alone (10 mg ⅐ kg Ϫ1 bolus ϩ 10 mg ⅐ kg bw Ϫ1 ⅐ h Ϫ1 , Sigma Aldrich; group 9), followed after 30 minutes by enalaprilat or after suprarenal aortic clamp (group 10). The increased RPP caused by L-NAME was corrected by a suprarenal aortic clamp.…”

Section: Methodsmentioning

confidence: 99%

Angiotensin II Type 2 Receptors and Nitric Oxide Sustain Oxygenation in the Clipped Kidney of Early Goldblatt Hypertensive Rats

et al. 2008

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Abstract-Angiotensin-converting enzyme inhibitors (ACEIs) decrease the glomerular filtration rate and renal blood flow in the clipped kidneys of early 2-kidney, 1-clip Goldblatt hypertensive rats, but the consequences for oxygenation are unclear. We investigated the hypothesis that angiotensin II type 1 or angiotensin II type 2 receptors or NO synthase mediate renal oxygenation responses to ACEI. Three weeks after left renal artery clipping, kidney function, oxygen (O 2 ) use, renal blood flow, renal cortical blood flow, and renal cortical oxygen tension (PO 2 ) were measured after acute administration of an ACEI (enalaprilat) and after acute administration of ACEI following acute administration of an angiotensin II type 1 or angiotensin II type 2 receptor blocker (candesartan or PD-123,319) or an NO synthase blocker (N G -nitro-L-arginine methyl ester with control of renal perfusion pressure) and compared with mechanical reduction in renal perfusion pressure to the levels after ACEI. The basal renal cortical PO 2 of clipped kidneys was significantly lower than contralateral kidneys (35Ϯ1 versus 51Ϯ1 mm Hg; nϭ40 each). ACEI lowered renal venous PO 2 , cortical PO 2 , renal blood flow, glomerular filtration rate, and cortical blood flow and increased the renal vascular resistance in the clipped kidney, whereas mechanical reduction in renal perfusion pressure was ineffective. 319 and N G -nitro-L-arginine methyl ester, but not candesartan, reduced the PO 2 of clipped kidneys and blocked the fall in PO 2 with acute ACEI administration. In conclusion, oxygen availability in the clipped kidney is maintained by angiotensin II generation, angiotensin II type 2 receptors, and NO synthase. This discloses a novel mechanism whereby angiotensin can prevent hypoxia in a kidney challenged with a reduced perfusion pressure. A reduced renal perfusion pressure (RPP) after clipping of a renal artery in the early (2-to 4-week) 2-kidney, 1-clip (2K,1C) rat model of Goldblatt hypertension increases angiotensin II (Ang II) concentrations in both kidneys 1 and causes Ang II-dependent hypertension. 2-4 A reduced renal tissue oxygen tension (PO 2 ) developing during prolonged infusion of Ang II 5-7 has been ascribed to reactive oxygen species and functional NO deficiency. Prolonged administration of the antioxidant drug Tempol, but not the angiotensin receptor blocker (ARB) candesartan, restores renal tissue PO 2 in a rat model of early 2K,1C hypertension. 5 This may be important, because renal hypoxia, and episodes of renal ischemia, may contribute to hypertension 8 and progressive kidney disease. 9 On the other hand, acute infusions of Ang II into rats increase renal NO generation and increase the dependency of renal blood flow (RBF) on NO. 10,11 Moreover, studies in the early 2K,1C rat model [12][13][14] have shown that the acute administration of an angiotensin-converting enzyme inhibitor (ACEI), or nonselective angiotensin receptor blockade with saralasin, reduces the RBF, and thereby the renal oxygen (O 2 ) delivery, and the glom...

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“…On the other hand, Duke et al (2005) obtained results suggesting that AT 1 receptors mediate renal medullary vasodilatation, possibly associated with the release of NO and PGs, which is opposed by AT 2 receptor activation, and in rats with two-kidney, one-clip hypertension, AT 2 -receptor activation tonically constricts the medullary circulation.…”

Section: In Vivo Study In Ratsmentioning

confidence: 96%

Interaction of Endothelial Nitric Oxide and Angiotensin in the Circulation

2007

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AT₂ receptors mediate tonic renal medullary vasoconstriction in renovascular hypertension

Cited by 26 publications

References 43 publications

Renal medullary tissue oxygenation is dependent on both cortical and medullary blood flow

Renal medullary tissue oxygenation is dependent on both cortical and medullary blood flow

Angiotensin II Type 2 Receptors and Nitric Oxide Sustain Oxygenation in the Clipped Kidney of Early Goldblatt Hypertensive Rats

Interaction of Endothelial Nitric Oxide and Angiotensin in the Circulation

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AT2 receptors mediate tonic renal medullary vasoconstriction in renovascular hypertension

Cited by 26 publications

References 43 publications

Renal medullary tissue oxygenation is dependent on both cortical and medullary blood flow

Renal medullary tissue oxygenation is dependent on both cortical and medullary blood flow

Angiotensin II Type 2 Receptors and Nitric Oxide Sustain Oxygenation in the Clipped Kidney of Early Goldblatt Hypertensive Rats

Interaction of Endothelial Nitric Oxide and Angiotensin in the Circulation

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AT₂ receptors mediate tonic renal medullary vasoconstriction in renovascular hypertension