Renal medullary interstitial infusion of norepinephrine  in anesthetized rabbits: methodological considerations

Correia, Anabela G.; Bergström, Göran; Lawrence, Andrew J; Evans, Roger G.

doi:10.1152/ajpregu.1999.277.1.r112

Cited by 16 publications

(28 citation statements)

References 16 publications

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“…Because these vasoconstrictors can be accumulated in ischemic kidney and stimulate medullary NO production, it is possible that decreases in medullary cGMP levels during reductions in RBF are partially buffered. Although other possibilities cannot be ruled out, our results support the hypothesis based on the results of previous studies (5,7,11,29,38,40) that the lesser responses of medullary cGMP to reductions in RBF may play an important role in protecting the renal medulla from ischemic injury.…”

Section: Discussionsupporting

confidence: 91%

“…Another possibility is that acute changes in blood flow differentially influenced NO-mediated cGMP production in the cortex and medulla. Recent studies have suggested norepinephrine (5,11,38), angiotensin II (40), and arginine vasopressin (7,29) receptor-mediated activation of NOS predominantly in the renal medulla. Because these vasoconstrictors can be accumulated in ischemic kidney and stimulate medullary NO production, it is possible that decreases in medullary cGMP levels during reductions in RBF are partially buffered.…”

Section: Discussionmentioning

confidence: 99%

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Blood flow-dependent changes in renal interstitial guanosine 3′,5′-cyclic monophosphate in rabbits

Nishiyama¹,

Kimura²,

Fukui³

et al. 2002

American Journal of Physiology-Renal Physiology

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. Blood flow-dependent changes in renal interstitial guanosine 3Ј,5Ј-cyclic monophosphate in rabbits. Am J Physiol Renal Physiol 282: F238-F244, 2002. First published September 21, 2001 10.1152/ajprenal. 00087.2001.-We examined responses of renal interstitial guanosine 3Ј,5Ј-cyclic monophosphate (cGMP) to changes in renal perfusion pressure (RPP) within and below the range of renal blood flow (RBF) autoregulation. A microdialysis method was used to monitor renal cortical and medullary interstitial cGMP levels in anesthetized rabbits. RPP was reduced in two steps: from ambient pressure (89 Ϯ 3 mmHg) to 70 Ϯ 2 mmHg (step 1) and then to 48 Ϯ 3 mmHg (step 2). RBF was maintained in step 1 but was significantly decreased in step 2 from 2.94 Ϯ 0.23 to 1.47 Ϯ 0.08 ml⅐min Ϫ1 ⅐g Ϫ1. Basal interstitial concentrations of cGMP were significantly lower in the cortex than in the medulla (12.1 Ϯ 1.4 and 19.9 Ϯ 0.4 nmol/l, respectively). Cortical and medullary cGMP did not change in step 1 but were significantly decreased in step 2, with significantly less reduction in cGMP concentrations in the medulla than in the cortex (Ϫ25 Ϯ 3 and Ϫ44 Ϯ 3%, respectively). Over this pressure range, changes in cortical and medullary cGMP were highly correlated with changes in RBF (r ϭ 0.94, P Ͻ 0.005 for cortex; r ϭ 0.82, P Ͻ 0.01 for medulla). Renal interstitial nitrate/nitrite was not changed in step 1 but was significantly decreased in step 2 (Ϫ38 Ϯ 2% in cortex and Ϫ20 Ϯ 2% in medulla). Nitric oxide synthase inhibition with N G -nitro-L-arginine methyl ester (L-NAME, 30 mg/kg bolus, 50 mg⅐kg Ϫ1 ⅐h Ϫ1 iv infusion) significantly decreased RBF (by Ϫ46 Ϯ 4%) and interstitial concentrations of cGMP (Ϫ27 Ϯ 4% in cortex and Ϫ22 Ϯ 4% in medulla, respectively). During L-NAME treatment, renal interstitial concentrations of cGMP in the cortex and medulla were similarly not altered in step 1. However, L-NAME significantly attenuated cGMP responses to a reduction in RPP in step 2. These results indicate that acute changes in RBF result in alterations in nitric oxide-dependent renal interstitial cGMP levels, with differential effects in the medulla compared with the cortex. renal interstitium; nitric oxide; renal blood flow; renal perfusion pressure; microdialysis NITRIC OXIDE (NO) is synthesized locally in the kidneys and plays a critical role in regulating renal hemodynamics as well as in sodium and water reabsorption through activation of soluble guanylate cyclase, which leads to accumulation of guanosine 3Ј,5Ј-cyclic monophosphate (cGMP) (19,20,23,27,(33)(34)(35)(36). One of the important mechanisms of NO-mediated cGMP production is controlled by alteration of shear stress (1, 3, 6, 9, 22), which is influenced by the fluid flow rate, fluid viscosity, and vessel diameter (1). Studies with isolated rat perfused kidneys (6) showed that increasing perfusate viscosity dilates the renal vasculature, and this is attenuated by treatment with NO synthase (NOS) inhibition. Using isolated rabbit afferent arterioles, Juncos et al. (9) demonstrated that endoth...

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Blood flow-dependent changes in renal interstitial guanosine 3′,5′-cyclic monophosphate in rabbits

Nishiyama¹,

Kimura²,

Fukui³

et al. 2002

American Journal of Physiology-Renal Physiology

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“…The left kidney was exposed via a flank incision and placed in a cup secured to the operating table. Catheters was placed in the left ureter and left renal vein (6). The kidney was denervated, and a transit-time ultrasound flow probe (type 2SB; Transonic Systems, Ithaca, NY) was placed around the renal artery for measurement of RBF.…”

Section: Animalsmentioning

confidence: 99%

Factors that render the kidney susceptible to tissue hypoxia in hypoxemia

Evans

Goddard

Eppel

et al. 2011

American Journal of Physiology-Regulatory, Integrative and Comp

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Evans RG, Goddard D, Eppel GA, O'Connor PM. Factors that render the kidney susceptible to tissue hypoxia in hypoxemia. Am J Physiol Regul Integr Comp Physiol 300: R931-R940, 2011. First published January 19, 2011 doi:10.1152/ajpregu.00552.2010To better understand what makes the kidney susceptible to tissue hypoxia, we compared, in the rabbit kidney and hindlimb, the ability of feedback mechanisms governing oxygen consumption (V O2) and oxygen delivery (DO 2 ) to attenuate tissue hypoxia during hypoxemia. In the kidney (cortex and medulla) and hindlimb (biceps femoris muscle), we determined responses of whole organ blood flow and V O2, and local perfusion and tissue PO2, to reductions in DO2 mediated by graded systemic hypoxemia. Progressive hypoxemia reduced tissue PO2 similarly in the renal cortex, renal medulla, and biceps femoris. Falls in tissue PO2 could be detected when arterial oxygen content was reduced by as little as 4 -8%. V O2 remained stable during progressive hypoxemia, only tending to fall once arterial oxygen content was reduced by 55% for the kidney or 42% for the hindlimb. Even then, the fall in renal V O2 could be accounted for by reduced oxygen demand for sodium transport rather than limited oxygen availability. Hindlimb blood flow and local biceps femoris perfusion increased progressively during graded hypoxia. In contrast, neither total renal blood flow nor cortical or medullary perfusion was altered by hypoxemia. Our data suggest that the absence in the kidney of hyperemic responses to hypoxia, and the insensitivity of renal V O2 to limited oxygen availability, contribute to kidney hypoxia during hypoxemia. The susceptibility of the kidney to tissue hypoxia, even in relatively mild hypoxemia, may have important implications for the progression of kidney disease, particularly in patients at high altitude or with chronic obstructive pulmonary disease. hyperemia; hypoxia; ischemia; kidney circulation; oxygen tension; skeletal muscle ONE OF THE GREAT PARADOXES of physiology is the susceptibility of the kidney to tissue hypoxia. The kidneys are among the most highly perfused organs in the body, receiving approximately one-quarter of the cardiac output at rest yet comprise Ͻ1% of total body weight (14). Thus renal oxygen delivery (DO 2 ) greatly exceeds oxygen consumption (V O 2 ). Yet the kidney is extremely susceptible to hypoxic damage, which in turn appears to be a crucial event in the pathogenesis of chronic kidney disease (8,19,32,35) and acute kidney injury (7, 20, 24) of diverse etiology. Therefore, it is imperative that we improve our understanding of the structural and functional characteristics of the kidney that make it susceptible to development of hypoxia.Most organs respond to a reduction in oxygenation by increasing local blood flow and so DO 2 (14). The increased DO 2 then acts to increase tissue oxygenation and so attenuate development of hypoxia and tissue injury. In this regard, the control of blood flow to the kidney is unique in that it appears to be dominated by the func...

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“…In 14 rabbits, medullary infusion catheters were acutely positioned laterally, 10 mm either side of the laser-Doppler flow probe, and advanced so that their tips lay 8.5 mm below the cortical surface (at the junction of the outer and inner stripes of the outer medulla). 5 The extracorporeal circuit was then established, and RAP was set at Ϸ65 …”

Section: Extracorporeal Circuitmentioning

confidence: 99%

“…To this end, we made use of our recent observation that medullary interstitial infusion of norepinephrine (NE) reduces MBF twice as much as CBF, whereas intravenous NE reduces only CBF. 5 Therefore, we compared the effects of medullary interstitial infusion and intravenous infusion of NE on antihypertensive responses to increased RAP. Thus, using this experimental design, we could control for the effects of NE exerted outside the renal medulla in a way that was not possible in our previous experiment with the V 1 -agonist.…”

mentioning

confidence: 99%

Effects of Renal Medullary and Intravenous Norepinephrine on Renal Antihypertensive Function

et al. 2000

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Abstract-Increasing renal arterial pressure activates at least 3 antihypertensive mechanisms: reduced renin release, pressure natriuresis, and release of a putative renal medullary depressor hormone. To examine the role of renal medullary perfusion in these mechanisms, we tested the effects of the infusion of norepinephrine, either infusion into the renal medullary interstitium or intravenous infusion, on responses to increased renal arterial pressure in pentobarbital-anesthetized rabbits. We used an extracorporeal circuit, which allows renal arterial pressure to be set to any level above or below systemic arterial pressure. With renal arterial pressure initially set at 65 mm Hg, intravenous and medullary interstitial norepinephrine (300 ng ⅐ kg Ϫ1 ⅐ min Ϫ1 ) similarly increased mean arterial pressure (by 12% to 17% of baseline) and reduced total renal blood flow (by 16% to 17%) and cortical perfusion (by 13% to 19%), but only medullary norepinephrine reduced medullary perfusion (by 28%). When renal arterial pressure was increased to Ϸ160 mm Hg, in steps of Ϸ65 mm Hg, urine output and sodium excretion increased exponentially, and plasma renin activity and mean arterial pressure fell. Medullary interstitial but not intravenous norepinephrine attenuated the increased diuresis and natriuresis and the depressor response to increased renal arterial pressure. This suggests that norepinephrine can act within the renal medulla to inhibit these renal antihypertensive mechanisms, perhaps by reducing medullary perfusion. These observations support the concept that medullary perfusion plays a critical role in the long-term control of arterial pressure by its influence on pressure diuresis/natriuresis mechanisms and also by affecting the release of the putative renal medullary depressor hormone. Key Words: kidney medulla Ⅲ laser-Doppler flowmetry Ⅲ norepinephrine Ⅲ natriuresis Ⅲ renal circulation I t has been hypothesized that the level of medullary blood flow (MBF) is an important determinant of urinary sodium excretion (U Na ϩ V) and, indeed, may be the key initiating factor in the pressure natriuresis response. 1 In turn, the impact of MBF on the pressure natriuretic mechanism provides an explanation for the effects of chronic changes in MBF on the long-term control of arterial pressure. 1 Thus, in rats, chronic reductions in MBF shift the pressure natriuresis relation toward higher pressures and lead to hypertension in normotensive animals. Conversely, chronic increases in MBF shift the pressure natriuresis relation toward lower pressures and ameliorate hypertension in spontaneously hypertensive rats. 1 From studies using an extracorporeal circuit in anesthetized rabbits, 2 we recently obtained preliminary evidence indicating that influences on the release and/or actions of the putative renal medullary depressor hormone might also contribute to the impact of MBF on the long-term control of arterial pressure. In this model, 3 major renal antihypertensive mechanisms can be studied simultaneously. Thus, when renal arterial ...

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Renal medullary interstitial infusion of norepinephrine in anesthetized rabbits: methodological considerations

Cited by 16 publications

References 16 publications

Blood flow-dependent changes in renal interstitial guanosine 3′,5′-cyclic monophosphate in rabbits

Blood flow-dependent changes in renal interstitial guanosine 3′,5′-cyclic monophosphate in rabbits

Factors that render the kidney susceptible to tissue hypoxia in hypoxemia

Effects of Renal Medullary and Intravenous Norepinephrine on Renal Antihypertensive Function

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