Variable responses of regional renal oxygenation and perfusion to vasoactive agents in awake sheep

Calzavacca, Paolo; Evans, Roger G.; Bailey, Michael; Bellomo, Rinaldo; May, Clive

doi:10.1152/ajpregu.00228.2015

Cited by 40 publications

(38 citation statements)

References 29 publications

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“…In healthy conscious sheep, infusion of angiotensin II did not reduce renal cortical or medullary perfusion, which was in contrast to the intra‐renal vasoconstrictor effects seen with norepinephrine . In a recent study of established ovine septic AKI, angiotensin II used as a primary vasopressor was shown to effectively restore blood pressure and transiently increase renal function, in a manner similar to that seen during infusion of norepinephrine (Figure ) .…”

Section: Catecholamine‐sparing Strategies For Septic Shock and Acute mentioning

confidence: 93%

“…In healthy sheep, intravenous infusion of norepinephrine dose‐dependently reduced both renal cortical and medullary tissue oxygenation, despite preserved RBF and RDO 2. In septic sheep with established AKI, restoration of blood pressure with clinically relevant high doses of norepinephrine (0.4‐0.8 μg/kg/min) exacerbated the underlying renal medullary ischemia and hypoxia (Figures and ) . These intra‐renal changes also occurred independently of changes in RBF and RDO 2 in response to norepinephrine infusion in septic sheep (Figure ) .…”

Section: High Doses Of Norepinephrine and The Renal Microcirculationmentioning

confidence: 94%

“…Similarly, in ovine septic AKI, low‐dose vasopressin (33 ng/min) has been reported to restore blood pressure and significantly improve renal function . In healthy conscious sheep, infusion of vasopressin preserved renal cortical and medullary tissue perfusion and oxygenation . Within the renal vasculature, the magnitude of the V 1 receptor‐mediated vasoconstriction by vasopressin has been demonstrated to be effectively modulated by vasodilator systems, such as nitric oxide and eicosanoids, specially in the renal cortex .…”

Section: Catecholamine‐sparing Strategies For Septic Shock and Acute mentioning

confidence: 96%

“…Within the renal vasculature, the magnitude of the V 1 receptor‐mediated vasoconstriction by vasopressin has been demonstrated to be effectively modulated by vasodilator systems, such as nitric oxide and eicosanoids, specially in the renal cortex . This may explain the better maintenance of intra‐renal perfusion and oxygenation in response to treatment with vasopressin when compared with norepinephrine in healthy sheep . Together, these findings suggest that vasopressin at lower doses may offer a degree of renoprotection in the setting of septic AKI compared with high doses of norepinephrine alone.…”

Section: Catecholamine‐sparing Strategies For Septic Shock and Acute mentioning

confidence: 97%

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Sepsis‐induced acute kidney injury: A disease of the microcirculation

et al. 2018

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AKI is a common complication of sepsis and is significantly associated with mortality. Sepsis accounts for more than 50% of the cases of AKI, with a mortality rate of up to 40%. The pathogenesis of septic AKI is complex, but there is emerging evidence that, at least in the first 48 hours, the defects may be functional rather than structural in nature. For example, septic AKI is associated with an absence of histopathological changes, but with microvascular abnormalities and tubular stress. In this context, renal medullary hypoxia due to redistribution of intra-renal perfusion is emerging as a critical mediator of septic AKI. Clinically, vasopressor drugs remain the cornerstone of therapy for maintenance of blood pressure and organ perfusion. However, in septic AKI, there is insensitivity to vasopressors such as norepinephrine, leading to persistent hypotension and organ failure. Vasopressin, angiotensin II, and, paradoxically, α -adrenergic receptor agonists (clonidine and dexmedetomidine) may be feasible adjunct therapies for catecholamine-resistant vasodilatory shock. In this review, we outline the recent progress made in understanding how these drugs may influence the renal microcirculation, which represents a crucial step toward developing better approaches for the circulatory management of patients with septic AKI.

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Section: Catecholamine‐sparing Strategies For Septic Shock and Acute mentioning

confidence: 93%

Section: High Doses Of Norepinephrine and The Renal Microcirculationmentioning

confidence: 94%

Section: Catecholamine‐sparing Strategies For Septic Shock and Acute mentioning

confidence: 96%

Section: Catecholamine‐sparing Strategies For Septic Shock and Acute mentioning

confidence: 97%

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Sepsis‐induced acute kidney injury: A disease of the microcirculation

et al. 2018

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“…Angiotensin‐II (AngII) induces constriction of efferent arterioles causing hypoperfusion of post‐glomerular peritubular capillaries, thus decreasing renal oxygen delivery (Calzavacca et al . ). Glomerular filtration rate (GFR) is usually maintained under such conditions (Treeck et al .…”

Section: Introductionmentioning

confidence: 97%

Exogenous and endogenous angiotensin‐II decrease renal cortical oxygen tension in conscious rats by limiting renal blood flow

Emans

Janssen

Pinkham

et al. 2016

The Journal of Physiology

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Key points Our understanding of the mechanisms underlying the role of hypoxia in the initiation and progression of renal disease remains rudimentary.We have developed a method that allows wireless measurement of renal tissue oxygen tension in unrestrained rats.This method provides stable and continuous measurements of cortical tissue oxygen tension (PO2) for more than 2 weeks and can reproducibly detect acute changes in cortical oxygenation.Exogenous angiotensin‐II reduced renal cortical tissue PnormalO2 more than equi‐pressor doses of phenylephrine, probably because it reduced renal oxygen delivery more than did phenylephrine.Activation of the endogenous renin–angiotensin system in transgenic Cyp1a1Ren2 rats reduced cortical tissue PnormalO2; in this model renal hypoxia precedes the development of structural pathology and can be reversed acutely by an angiotensin‐II receptor type 1 antagonist.Angiotensin‐II promotes renal hypoxia, which may in turn contribute to its pathological effects during development of chronic kidney disease. AbstractWe hypothesised that both exogenous and endogenous angiotensin‐II (AngII) can decrease the partial pressure of oxygen (PO2) in the renal cortex of unrestrained rats, which might in turn contribute to the progression of chronic kidney disease. Rats were instrumented with telemeters equipped with a carbon paste electrode for continuous measurement of renal cortical tissue PnormalO2. The method reproducibly detected acute changes in cortical oxygenation induced by systemic hyperoxia and hypoxia. In conscious rats, renal cortical PnormalO2 was dose‐dependently reduced by intravenous AngII. Reductions in PnormalO2 were significantly greater than those induced by equi‐pressor doses of phenylephrine. In anaesthetised rats, renal oxygen consumption was not affected, and filtration fraction was increased only in the AngII infused animals. Oxygen delivery decreased by 50% after infusion of AngII and renal blood flow (RBF) fell by 3.3 ml min−1. Equi‐pressor infusion of phenylephrine did not significantly reduce RBF or renal oxygen delivery. Activation of the endogenous renin–angiotensin system in Cyp1a1Ren2 transgenic rats reduced cortical tissue PnormalO2. This could be reversed within minutes by pharmacological angiotensin‐II receptor type 1 (AT1R) blockade. Thus AngII is an important modulator of renal cortical oxygenation via AT1 receptors. AngII had a greater influence on cortical oxygenation than did phenylephrine. This phenomenon appears to be attributable to the profound impact of AngII on renal oxygen delivery. We conclude that the ability of AngII to promote renal cortical hypoxia may contribute to its influence on initiation and progression of chronic kidney disease.

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