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Review
. 2013 Mar;61(3):673-80.
doi: 10.1161/HYPERTENSIONAHA.111.00241.

The intrarenal renin-angiotensin and dopaminergic systems: control of renal sodium excretion and blood pressure

Robert M Carey  1
Affiliations
Review

The intrarenal renin-angiotensin and dopaminergic systems: control of renal sodium excretion and blood pressure

Robert M Carey. Hypertension. 2013 Mar.
No abstract available

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Figures

Figure 1
Figure 1
Evidence for a functional intrarenal renin-angiotensin system in uninephrectomized conscious dogs. Panel A: Renal blood flow (RBF); Panel B: glomerular filtration rate (GFR); Panel C: Urinary Na+ excretion (UNaV) in response to intrarenal arterial administration of ACE inhibitor SQ-20881 (2 μg/kg/min) or Ang receptor blocker P-113 (saralasin; 2 μg/kg/min). Control vehicle infusion, white bars; experimental agent infusion, black bars. Sham data include vehicle infusion only. Data are expressed as mean ± 1 SE. Adapted from Kimbrough HM et al. Circ Res. 1977;40:174–178.
Figure 2
Figure 2
Validation of an independent functional intrarenal renin-angiotensin system in uninephrectomized conscious dogs. Estimated renal plasma flow (ERPF; Panel A), glomerular filtration rate (GFR; Panel B), urine flow rate (UVOL; Panel C) and urinary Na+ excretion (UNaV; Panel D) in response to low-dose intrarenal arterial infusion of Ang receptor blocker saralasin (0.07 μg/kg/min). Numbers on abscissa represent 20 min clearance periods. Adapted from Levens NR et al. Endocrinology. 1983:112:43–49 with permission.
Figure 3
Figure 3
Ang II releases renal bradykinin (BK) by AT2R activation. Renal interstitial fluid BK levels in response to intravenous infusion of Ang II, Losartan, an AT1R antagonist; PD, PD-123319, an AT2R antagonist, and combinations in Sprague-Dawley rats. Control vehicle infusions, white bars; experimental agent infusions, black bars. Data are expressed as mean ± 1 SE. * P<0.0001 from control; + P<0.05, ++P<0.0001 from Ang II alone. Data from Siragy HM et al. Am J Physiol Reg Int Comp Physiol. 1996;271:R1090–R1095 and Siragy HM and Carey RM, Hypertension 1999;33:1237–1242.
Figure 4
Figure 4
Ang II releases renal cyclic GMP (cGMP) by AT2R activation. Renal interstitial fluid cGMP levels in response to intravenous infusion of Ang II; Losartan, an AT1R antagonist; PD, PD-123319, an AT2R antagonist, and combinations in Sprague-Dawley rats. Control vehicle infusion data, white bars; experimental agent infusion, black bars. Data represent mean ± 1 SE. * P<0.001 from vehicle or time control; + P<0.001 from Ang II alone. Adapted from Siragy *HM and Carey RM. J Clin Invest. 1996;97:1978–1982 and Siragy HM and Carey RM. J Clin Invest. 1997:100:264–269 with permission.
Figure 5
Figure 5
Ang III is the preferred endogenous AT2R agonist mediating natriuresis. Urinary Na+ excretion (UNaV) in anesthetized Sprague-Dawley rats in response to direct renal interstitial infusion of vehicle (white bars), Ang II (black bars), Ang III (gray bars) or Ang III +PD (PD-123319, an AT2R antagonist) (striped bars). Data are expressed as mean ± 1 SE. * P<0.05, ** P<0.01, *** P<0.001 from time control. Adapted from Padia SH et al. Hypertension. 2006.
Figure 6
Figure 6
Oral fenoldopam lowers BP in hypertensive humans. BP responses to oral fenoldopam (SKF-82526-J) in patients with primary hypertension. Data are expressed as mean ± 1 SE. Adapted from Carey RM et al. J Clin Invest. 1984;74:2198–2207 with permission.
Figure 7
Figure 7
Evidence that intrarenal dopamine controls renal Na+ excretion by a paracrine mechanism acting at the level of the renal tubule. Urinary Na+ excretion (UNaV) in uninephrectomized conscious dogs infused intrarenally with D1-LIKE receptor antagonist SCH-23390. Data are expressed as mean ± 1 SE. * P<0.001, ** P<0.0001 from pre-control; † P<0.05, †† P<0.01 from time control. Adapted from Siragy HM et al. Am J Physiol Renal Physiol. 1988;257:F469–F477 with permission.
Figure 8
Figure 8
Intrarenal interstitial fenoldopam-induced natriruesis is abolished by intrarenal D1-LIKE receptor antagonist SCH-23390 (SCH) or AT2R antagonist PD-123319 (PD) in anesthetized, uninephrectomized Sprague-Dawley rats. Vehicle infusion, white bars; fenoldopam (1 μg/kg/min) infusion, black bars; fenoldopam + PD infusion, gray bars; fenoldopamn + SCH infusion, striped bars. Data are expressed as mean ± 1 SE. Numbers on the abscissa refer to experimental one-hour periods. * P<0.01, ** P<0.001 from vehicle control. Adapted from Salomone LJ et al. Hypertension. 2007;49:155–161 and Padia SH et al. Hypertension. 2012;59:437–445.
See this image and copyright information in PMC

References

    1. Carey RM, Siragy HM. Newly recognized components of the renin-angiotensin system: potential roles in cardiovascular and renal disease. Endocr Rev. 2003;24:261–267. - PubMed
    1. deGasparo M, Catt KJ, Inagami T, Wright JW, Unger T International Union of Pharmacology. XXIII. The angiotensin II receptors. Pharmacol Rev. 2000;53:415–472. - PubMed
    1. Carey RM. Cardiovascular and renal regulation by the angiotensin type 2 receptor: the AT2 receptor comes of age. Hypertension. 2005;45:840–844. - PubMed
    1. Jones ES, Vinh A, McCarthy CA, Gaspari TA, Widdop RE. AT2 receptors: functional relevance in cardiovascular disease. Pharmacol Ther. 2008;120:292–316. - PMC - PubMed
    1. Carey RM. Theodore Cooper Lecture. Renal dopamine system: paracrine regulator of sodium homeostasis and blood pressure. Hypertension. 2001;38:297–302. - PubMed

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