Renal and adrenal responses to hypoxemia during angiotensin-converting enzyme inhibition in lambs.

Abstract

SUMMARY. Chronically catheterized lambs (4-37 days postnatal age) (n =35) were studied to test the hypothesis that the products of angiotensin-converting enzyme activity are involved in renal and adrenal responses to normocapnic hypoxemia in immature lambs. Arterial angiotensin II (from 111.0 ± 38.8 to 71.0 ± 38.8 pg/ml, P < 0.01) and aldosterone (from 128.0 ± 98.0 to 62.1 ± 27.9 pg/ml, P < 0.01) concentrations were significantly decreased and vasopressor responses to angiotensin I were greater than 90% inhibited by continuous intravenous infusion of angiotensin-converting enzyme inhibitor (captopril, 2.5 /ig/kg/min, n =16). Baseline mean arterial pressure (64 ± 14 vs. 78 ± 9 mmHg) and urinary sodium excretion rate (UN 8 V 3.04 ± 2.83 vs. 15.00 ± 20.00 fiEq//min) were significantly (P < 0.05) decreased in captopril-treated lambs vs. control lambs. Baseline arterial plasma renin activity was significantly (P < 0.01) increased in captopril-treated vs. control lambs (8.6 ± 9.0 vs. 100.0 ± 64.0 ng/ml per hr). Normocapnic hypoxemia (P02 38 ± 6 torr for 30 minutes) during captopril infusion was associated with no significant (P > 0.05) changes in renal hemodynamics and function, including glomerular filtration rate (from 0.34 ± 0.24 to 0.35 ± 0.25 ml/min per g). Urinary prostaglandin E excretion rate (from 0.655 ± 0.703 to 1.310 ± 1.020 ng/min) and adrenal blood flow (from 2.67 ± 1.69 to 6.24 ± 3.73 ml/min per g) increased significantly (P < 0.05) under these conditions. Arterial epinephrine (from 0.11 ± 0.07 to 1.1 ± 1.8 ng/ml), norepinephrine (0.48 ± 0.38 to 3.2 ± 5.4 ng/ml), and arginine vasopressin (from 5.11 ± 2.20 to 10.70 ± 8.61 jiU/ml) also increased significantly (P < 0.05) in response to hypoxemia during angiotensin-converting enzyme inhibition with captopril. None of these responses to hypoxemia were significantly different from that of uninhibited (control) lambs (n=19). In contrast, cortisol response to hypoxemia was significantly (P < 0.05) less in captopril-treated lambs (captopril vs. control, -1.00 ± 1.90 vs. 3.40 ± 3.30 /ig/dl). These data suggest that the products of angiotensin-converting enzyme activity are not important regulators of renal responses to hypoxemia, but may be involved in cortisol responses to normocapnic hypoxemia in immature lambs. (Circ Res 52: 179-187, 1983)

The Newborn Rabbit: A Model for Studying Hypoxemia-Induced Renal Changes

“…While respiratory distress syndrome has been uniformly associated with a fall in di uresis in human neonates [6,12,20], studies in hypoxemic animal models disclosed either unchanged [21,23] or increased urine flow rates [1,15,17], The urine flow rate response to hypoxemia has been shown to vary according to postnatal age [21], to the extent of the decline in GFR and to in creased vasopressin secretion rate [2,8,14,21,23]. In the newborn rabbit, a stable diuresis despite a declining GFR points to a reduction of tubular water reabsorption, as suggested by a significant fall in the U/P inulin ratio.…”

“…RBF, renal vascular resistance and urine flow rate did not change significantly. In comparison with other immature animal species the newborn rabbit appears a valuable and inexpensive model for the study of acute hypoxemiainduced renal changes.Respiratory distress syndrome and birth asphyxia, hypoxemic conditions frequently encountered in newborn infants, can be asso ciated with an impairment in renal functions and renal failure [6,9,12,19,20], The pre cise role of hypoxemia in the absence of aci dosis and hypercarbia cannot be fully estab lished in human neonates [12] and has been assessed in neonatal animal models such as lambs [16,21,22,23], piglets [17] and pup pies [15]. However, the hypocarbia reported in some studies [15,17], as well as interspe cies variations and different experimental conditions could account for the discrepan cies reported in the literature.…”

Renal Hemodynamic Responses to Hypoxemia during Development: Relationships to Circulating Vasoactive Substances

“…Induction of anesthesia of the ewe and fetal surgical procedures were performed as described previously (12, 29-3 1). Anesthesia and surgical procedures in neonatal lambs were also performed as described previously (9,15). Briefly, in the fetus, catheters were placed in one femoral artery and a femoral vein with catheter tips located in the distal abdominal aorta and inferior vena cava, respectively.…”

“…An independent lower body reference sample was obtained by withdrawal of blood (Harvard infusion/withdrawal pump) through a femoral arterial catheter at a rate of 2.91 ml/min (fetuses) or 1.94 ml/min (neonates) for a period of 3 min starting approximately 20 s before the microspheres injection (32). After the microspheres injection, systemic hypoxemia was produced by directing an 1 1.1 + 0.0 1 % oxygen in nitrogen gas mixture (Air Products Co.) into a clear plastic bag that was placed over the head of the ewe or neonatal lamb, as described previously (9,12,15). During the first few minutes of administration of the oxygen deficient inhaled gas mixture, the gas mixture flow rate was adjusted according to the blood gas measurements in order to maintain pH and pC02 values within the normal range.…”

“…Major hemodynamic adjustments occur in response to perinatal asphyxia or hypoxemia, including response of RBF and RVR (2)(3)(4)(5)(6)(7)(8)(9). Numerous circulating vasoactive mediators appear in increased concentration in blood in response to perinatal hypoxemia, including E (10-16), NE (10)(11)(12)(13)(14)(15)(16), AVP (9,12,(15)(16)(17)(18)(19)(20), and PRA (9,12,15,21). Furthermore, previous work has demonstrated hemodynamic and renal responses to hypoxemia that appear to be developmental age dependent (9,22,23).…”