Plasma levels of the vasodilator atrial natriuretic peptide (ANP) are markedly elevated during the first days of life and decrease by the 2nd week [17]. High ANP levels are probably involved in reducing the expanded extracellular volume, characteristic of the fetus and the newborn [18]. However, the natriuretic and diuretic effects of ANP infusion in the newborn rabbit are blunted compared with the response in the adult rabbit [19]. This is probably the result of low fetal and neonatal renal ANP receptor-binding capacity [20].
The vasodilator and diuretic peptide bradykinin (BK) is produced by kallikrein (KK) enzyme in the kidney (connecting tubule). BK exerts its renal effects via B2 receptors, the expression of which is higher in neonatal than adult kidneys, suggesting a developmental role of this peptide [21]. The renal expression and urinary ex-
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cretion of KK is low at birth, but rises rapidly in the postnatal period. The excretion of KK correlates with the rise in RBF [22, 23]. In the newborn rabbit, BK maintains renal vasodilation, as evidenced by the renal vasoconstrictor effect of BK B, receptor blockade [24].
Newborn infants have high circulating plasma levels of vasodilatory prostaglandins (PGs) that counteract the highly activated vasoconstrictor state of the neonatal renal microcirculation [7]. The deleterious renal vasocon-strictive effect of PG synthesis inhibitors, in clinical use for pharmacological closure of patent ductus arteriosus (PDA), illustrates the protective role of PGs in the immature kidney [25]. These PGs are essential in pathological conditions when vasoconstrictor forces are stimulated, such as in congestive heart failure (CHF) [26].
Endothelium-derived NO is also an important intrare-nal vasodilator in the developing kidney, counteracting the activated renal vasoconstrictor forces [27, 28]. The recently described potent vasodilator peptide adren-omedullin (AM) decreases RVR and increases RBF, while in animal models GFR does not change [29]. In human cord blood, high AM levels were detected and were significantly correlated with the cord arterial pH [30, 31]. Similar to other endogenous vasodilating agents, AM is theoretically a protective factor in pathological conditions affecting the newborn kidney.
methacin achieves an improvement in systemic circulation, while it may impair renal perfusion.
Conditions that may
threaten neonatal renal function
The major, primary, secondary, and/or iatrogenic conditions causing VMNP are summarized in Table 1. Here we will briefly discuss some clinical aspects of these conditions and whenever possible we will indicate the pathways that mediate VMNP in the various disease states. An understanding of these pathophysiological mechanisms may lead to prevention in the future.
Hypovolemia
More than 80% of all cases of ARF in the neonate are due to prerenal causes, such as a contraction of blood volume with or without failure of the cardiac pump [3]. VMNP can be caused by primary cardiac hypotension and hypovolemia or may be the end result of hypotension-stimulated release of mediators such as All, vaso-pressin, and catecholamines in a variety of pathophysiological situations [34].
Vasomotor nephropathy
Vasomotor nephropathy (VMNP) is a term indicating renal dysfunction, with or without parenchymal damage, due to reduced renal perfusion. VMNP, the subject of this review, is often used as an imprecise alternative for prerenal ARF. Continued VMNP can lead to irreversible renal damage. Primary renal and postrenal ARF will not be discussed in this paper. For a discussion of the various pathogenetic mechanisms underlying the development of ARF and/or of the nature of the secondary renal cellular damage seen after prolonged prerenal ARF, the interested reader is referred to recent papers [32,
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