Does Endothelin-1 Mediate the Hypoxemia-lnduced Renal Dysfunction in Newborn Rabbits?

Semama, Denis S.; Thonney, M.; Guignard, Jean‐Pierre

doi:10.1159/000244167

Cited by 14 publications

(10 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…As previously shown in newborn rabbits (4,(7)(8)(9)(10)(11)19), as well as lambs and puppies (33)(34)(35), acute normocapnic hypoxemia in the present study was associated with a significant drop in GFR, together with a concomitant decrease in RBF, MAP, and diuresis, and a significant increase in RVR. Administration of the specific A 1 antagonist DPCPX totally prevented the well-documented hypoxemia-induced fall in GFR and diuresis; both parameters were not modified from the control period to the experimental hypoxemia plus DPCPX periods, although MAP remained significantly decreased.…”

Section: Map Heart Rate (Hr) Hematocrit (Htc) Plasma Protein Levsupporting

confidence: 88%

See 1 more Smart Citation

Renal Effects of Adenosine A1-Receptor Blockade with 8-Cyclopentyl-1,3-Dipropylxanthine in Hypoxemic Newborn Rabbits

et al. 2003

View full text Add to dashboard Cite

The key role of intrarenal adenosine in mediating the hypoxemic acute renal insufficiency in newborn rabbits has been well demonstrated using the nonspecific adenosine antagonist theophylline. The present study was designed to define the role of adenosine A 1 receptors during systemic hypoxemia by using the specific A 1 -receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). Renal function parameters were assessed in 31 anesthetized and mechanically ventilated newborn rabbits. In normoxia, DPCPX infusion induced a significant increase in diuresis (ϩ44%) and GFR (ϩ19%), despite a significant decrease in renal blood flow (RBF) (Ϫ22%) and an increase in renal vascular resistance (RVR) (ϩ37%). In hypoxemic conditions, diuresis (Ϫ19%), GFR (Ϫ26%), and RBF (Ϫ35%) were decreased, whereas RVR increased (ϩ33%). DPCPX administration hindered the hypoxemia-induced decrease in GFR and diuresis. However, RBF was still significantly decreased (Ϫ27%), whereas RVR increased (ϩ22%). In all groups, the filtration fraction increased significantly. The overall results support the hypothesis that, in physiologic conditions, intrarenal adenosine plays a key role in regulating glomerular filtration in the neonatal period through preferential A 1 -mediated afferent vasoconstriction. During a hypoxemic stress, the A 1 -specific antagonist DPCPX only partially prevented the hypoxemiainduced changes, as illustrated by the elevated RVR and drop in RBF. These findings imply that the contribution of intrarenal adenosine to the acute adverse effects of hypoxemia might not be solely mediated via the A 1 receptor. Adenosine is ubiquitous in the kidney. Intrarenal adenosine vasoconstricts the preglomerular vessels via the A 1 receptors, while dilating the efferent arterioles via the A 2 receptors. It thus affects GFR as well as RBF and its distribution within the kidney. In addition to its vascular actions, intrarenal adenosine modulates renal mechanisms, including TGF, renin release, and the tubular handling of electrolytes and water. Intrarenal adenosine also appears to be an important hemodynamic mediator in some models of vasomotor nephropathy, such as those induced by intramuscular glycerol injection (1), contrast media (2), cisplatin (3), or hypoxemia (4).In animal models as in humans, hypoxemia can lead to functional renal insufficiency (5-7). In the newborn rabbit, acute normocapnic hypoxemia induces renal hypoperfusion with decreased GFR and RBF (4, 7-9). The underlying mechanism of this hypoxemia-induced vasomotor nephropathy still remains controversial. The chemoreceptor-mediated reflex and/or the activation of vasoactive factors such as angiotensin II (AII) (9), endothelin (10), nitric oxide (8), or bradykinin (11) have been suggested to play a role.We previously demonstrated that the administration of theophylline, a nonspecific antagonist to adenosine receptors, ameliorates the hypoxemia-induced renal hemodynamic changes seen in the newborn rabbit model (4). Moreover, in neonates with respiratory distress syndrome (12)

show abstract

Section: Map Heart Rate (Hr) Hematocrit (Htc) Plasma Protein Levsupporting

confidence: 88%

“…The underlying mechanism of this hypoxemia-induced vasomotor nephropathy still remains controversial. The chemoreceptor-mediated reflex and/or the activation of vasoactive factors such as angiotensin II (AII) (9), endothelin (10), nitric oxide (8), or bradykinin (11) have been suggested to play a role.…”

mentioning

confidence: 99%

Renal Effects of Adenosine A1-Receptor Blockade with 8-Cyclopentyl-1,3-Dipropylxanthine in Hypoxemic Newborn Rabbits

et al. 2003

View full text Add to dashboard Cite

show abstract

“…Exogenous ET causes renal vasoconstriction in the newborn rabbit; this vasoconstriction is similar to that seen in hypoxemia [12]. The glomerular dysfunction of hypoxemic newborn rabbits is not prevented by pretreatment with ET antiserum [122]. ET may, however, play a role in other forms of neonatal renal failure (e.g., due to sepsis), and ET antagonists may therefore still prove to be useful protectors of ARF.…”

Section: Vasomotor Disturbancesmentioning

confidence: 89%

The stressed neonatal kidney: from pathophysiology to clinical management of neonatal vasomotor nephropathy

Tóth-Heyn¹,

Drukker

Guignard

2000

Pediatric Nephrology

Self Cite

191

115

View full text Add to dashboard Cite

The healthy term, and particularly the premature infant, is born with a very low glomerular filtration rate (GFR), controlled by a delicate balance of intrarenal vasoconstrictor and vasodilator forces. Vasoactive disturbances can easily further reduce the already low GFR. The newborn infant is thus prone to develop vasomotor nephropathy (VMNP) or acute renal failure (ARF). The main causes for ARF at this young age are prerenal mechanisms, and include hypotension, hypovolemia, hypoxemia perinatal asphyxia, and neonatal septicemia. Other causes include the administration of angiotensin converting enzyme inhibitors, indomethacin and tolazoline. The most-important factors governing the ultimate renal prognosis are the severity of the underlying disorder, the rapidity of an accurate diagnosis, prompt treatment, and avoidance of severe iatrogenic complications. The immediate treatment is of particular importance in VMNP, i.e., prerenal ischemic ARF, and consists of correcting abnormalities in fluid homeostasis and reduction of the complications of the acute azotemic state (uremia, hyperkalemia, acidosis, and hypertension). In severe and prolonged (established) ARF, temporary dialysis therapy may be indicated. Prerenal ARF with oliguria or anuria warrants immediate volume resuscitation. Special attention should be given to infants with congestive heart failure (CHF). The sick neonate with persistent oliguria and CHF should be treated with intravenous dopamine. Furosemide (FM) is the second line of therapy for babies with indomethacin-induced ARF. In most other conditions, the therapeutic effect of FM is limited to a transient increase in urine flow, without improving basic renal function. The special conditions of the maturing kidney have to be appreciated in order to protect babies from undue renal injury. With the increasing knowledge of the mechanisms governing the development of ARF, progress has been made in the development of new treatment modalities. For example theophylline, calcium antagonists, ATP-MgCl2, thyroxine, and a variety of cytokines may in the near future be used to prevent or ameliorate VMNP and/or recently established ARF. With a combination of time-honored and new therapeutic strategies, there may well be a brighter future for neonates with vasomotor, prerenal, ischemic ARF.

show abstract

“…Severe hypoxemia has been demonstrated to reduce RBF by increasing renal vascular resistance related to the activation of vasoactive factors such as angiotensin II, endothelin and a decrease in NO [63][64][65] . Hypercapnia was found to correlate inversely with RBF mainly by stimulating noradrenaline release and inducing vasoconstriction [66] .…”

Section: Mechanisms Of Ali-associated Kidney Injurymentioning

confidence: 99%

Kidney-Lung Crosstalk in the Critically Ill Patient

Rabb

Hassoun

2009

Blood Purif

View full text Add to dashboard Cite

Despite advances in renal replacement therapy, the mortality of acute kidney injury (AKI) has remained high, especially when associated with distant organ dysfunction such as acute lung injury (ALI). Mortality rates for combined AKI/ALI reach 80% in critically ill patients. While the clinical presentation of AKI-associated ALI is characterized by increased pulmonary edema, a defining feature of the syndrome, the AKI-induced lung effects extend beyond simple volume overload. Furthermore, ALI and associated mechanical ventilation frequently lead to a decline in renal hemodynamics, structure and function. New experimental data have emerged in recent years focusing on the interactive effects of kidney and lung dysfunction, and these studies have highlighted the pathophysiological importance of proinflammatory and proapoptotic pathways as well as the complex nature of interorgan crosstalk. This review will examine our current understanding of the deleterious kidney-lung crosstalk in the critically ill.

show abstract

Does Endothelin-1 Mediate the Hypoxemia-lnduced Renal Dysfunction in Newborn Rabbits?

Cited by 14 publications

References 21 publications

Renal Effects of Adenosine A1-Receptor Blockade with 8-Cyclopentyl-1,3-Dipropylxanthine in Hypoxemic Newborn Rabbits

Renal Effects of Adenosine A1-Receptor Blockade with 8-Cyclopentyl-1,3-Dipropylxanthine in Hypoxemic Newborn Rabbits

The stressed neonatal kidney: from pathophysiology to clinical management of neonatal vasomotor nephropathy

Kidney-Lung Crosstalk in the Critically Ill Patient

Contact Info

Product

Resources

About