Theophylline prevents the hypoxemia-induced renal hemodynamic changes in rabbits

Gouyon, Jean‐Bernard; Guignard, Jean‐Pierre

doi:10.1038/ki.1988.114

Cited by 121 publications

(93 citation statements)

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“…This water and sodium homeostasis during the neonatal period. The confirms other reports showing that the intrarenal infusion of renal hemodynamic effects of endothelin mimic some of the endothelin induced intense renal vasoconstriction without changes induced by acute hypoxemia in animal models ( 10,12) changing MBP, thus pointing to a local action of endothelin on as well as in human newborns (3 1). r his observation suggests the renal microcirculation (6,22).…”

Section: Discussionsupporting

confidence: 79%

Effects of Endothelin on Renal Function in Newborn Rabbits

Thonney

et al. 1993

Pediatr Res

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ABSTRACT. The renal effects of endothelin-1 were investigated in 16 anesthetized and mechanically ventilated newborn rabbits. Renal blood flow and glomerular filtration rate were determined by the clearance of para-aminohippuric acid and inulin, respectively. Each animal acted as its own control. In eight newborn rabbits, a bolus injection of 5 nmol.kg-' of endothelin-1 caused an initial fall in mean arterial blood pressure followed by a gradual, significant increase in mean arterial blood pressure that lasted for 45 min. The dramatic increase in renal vascular resistance (+28 f 4%) induced by endothelin led to a fall in glomerular filtration rate (-12 + 4%) and renal blood flow (-16 + 3%). In spite of the reduction of glomerular filtration rate and renal blood flow, urine flow and sodium excretion rates increased significantly (+20 f 5% and +49 f 9%, respectively). In eight additional newborn rabbits, a bolus injection of 1 nmol. kg-' of endothelin-a dose that usually induces marked renal and systemic vasoconstriction in adult models-did not affect systemic or renal hemodynamics. In conclusion, endothelin induces renal and systemic vasoconstriction and affects water and sodium homeostasis during the neonatal period. These effects occur under higher doses than those used in adult animals. This age difference in systemic and renal responsiveness is probably mediated by receptor immaturity and/or interference of high levels of counteracting hormones present during the neonatal period. (Pediatr Res 34: 120-123, 1993) Abbreviations CFR, glomerular filtration rate RBF, renal blood flow RPF, renal plasma flow FF, filtration fraction MBP, mean blood pressure RVR, renal vascular resistance PAH, paraaminohippuric acid V, urine flow rate UNaV, urinary sodium excretionThe immature kidney is exposed to various vasoactive systems such as the renin-angiotensin system, intrarenal adenosine, the prostaglandins, and atrial natriuretic peptide, which are hyper-

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Section: Discussionsupporting

confidence: 79%

Effects of Endothelin on Renal Function in Newborn Rabbits

Thonney

et al. 1993

Pediatr Res

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“…On the other hand, since 8-PT blocked the decrease in RVC and FBF during 10% 02, this indicates that locally released adenosine did contribute to the renal vasoconstriction induced by moderate hypoxia (see Spielman & Thompson, 1982). Similarly, theophylline blocked the renal vasoconstriction induced by systemic hypoxia in 3-to 12-day-old rabbit kittens (Gouyon & Guignard, 1988). However, as 8-PT had no effect on FVC or FBF during hypoxia, it seems locally released adenosine did not exert a dilator influence upon skeletal muscle vasculature.…”

Section: Responses Evoked In Newborn Pigletsmentioning

confidence: 99%

Postnatal development of the pattern of respiratory and cardiovascular response to systemic hypoxia in the piglet: the roles of adenosine.

Elnazir

Marshall

Kumar

1996

The Journal of Physiology

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1. In 3-day-old and 3-week-old spontaneously breathing piglets anaesthetized with Saffan, we have studied ventilatory and cardiovascular responses evoked by 5 min periods of hypoxia (breathing 10 and 6% 02). 2. In 3-day-old piglets both 10 and 6% 02 evoked an increase followed by a secondary fall in ventilation, a gradual tachycardia and a renal vasoconstriction, with an increase in femoral blood flow that was attributable to femoral vasodilatation. Arterial blood pressure rose initially but fell towards control values by the 5th minute of hypoxia.3. The stable adenosine analogue 2-chloroadenosine (2-CA; 30 mg kg-' i.v.) evoked bradycardia and renal vasoconstriction, but had no effect on femoral vasculature. These responses were blocked by the adenosine receptor antagonist 8-phenyltheophylline (8-PT; 8 mg kg-1 i.v.). 8-PT also abolished the secondary fall in ventilation evoked by 10 and 6% 02 and the renal vasoconstriction evoked by 10 % 02, but had no effect on the tachycardia, or on the femoral vascular response. 4. By contrast, in 3-week-old piglets both 10 and 6% 02 evoked a sustained increase in ventilation, tachycardia and a rise in arterial pressure with renal vasoconstriction, but no change in renal blood flow and substantial femoral vasodilatation with an increase in femoral blood flow. 2-CA evoked bradycardia and renal vasoconstriction, as in 3-day-old piglets, but also evoked pronounced femoral vasodilatation. 8-PT blocked these responses and the hypoxia-induced femoral vasodilatation, but had no significant effect on other components of the hypoxia-induced response. 5. We propose that there is postnatal development of the ventilatory and cardiovascular responses evoked by systemic hypoxia and of the role of locally released adenosine in these responses: at 3 days, adenosine released within the central nervous system and within the kidney is a major contributor to the secondary fall in ventilation and renal vasoconstriction, respectively, whereas at 3 weeks, adenosine makes little contribution to the ventilatory response, or renal vasoconstriction, but is largely responsible for hypoxia-induced vasodilatation in skeletal muscle.

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“…In the newborn rabbit, acute normocapnic hypoxemia induces renal hypoperfusion with decreased GFR and RBF (4,(7)(8)(9). The underlying mechanism of this hypoxemia-induced vasomotor nephropathy still remains controversial.…”

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confidence: 99%

“…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) or perinatal asphyxia (13), as in diuretic-dependent critically ill children (14), the use of theophylline improves diuresis and creatinine clearance.…”

mentioning

confidence: 99%

“…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).…”

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confidence: 99%

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

et al. 2003

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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)

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Theophylline prevents the hypoxemia-induced renal hemodynamic changes in rabbits

Cited by 121 publications

References 20 publications

Effects of Endothelin on Renal Function in Newborn Rabbits

Effects of Endothelin on Renal Function in Newborn Rabbits

Postnatal development of the pattern of respiratory and cardiovascular response to systemic hypoxia in the piglet: the roles of adenosine.

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

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