Comparison of the adrenal and renal responses to angiotensin II fetal lambs and adult sheep.

Robillard, J; Gómez, R. Ariel; VanOrden, D; Smith, Francine G.

doi:10.1161/01.res.50.1.140

Cited by 76 publications

(39 citation statements)

References 45 publications

(49 reference statements)

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“…For example, AT1 receptor gene expression in the kidney of sheep remains relatively constant throughout the latter part of gestation and early newborn period and decreases •10 days after birth (Robillard et al 1994), although the physiological consequences of this on renal vascular tone are not known. In mid-term fetal sheep, however, angiotensin II administration is associated with a reduction in renal blood flow measured using radiolabelled microspheres (Robillard et al 1982b), this effect being similar in fetal and adult sheep. Moreover, in our laboratory, we have shown in conscious lambs that administration of the angiotensin converting enzyme inhibitor, captopril, is associated with a marked decrease in renal blood flow .…”

Section: Discussionmentioning

confidence: 87%

Renin and Heart Rate Responses to Haemorrhage are Age Dependent in Conscious Lambs

Smith

Basati

Şener

et al. 2000

Experimental Physiology

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The present experiments were carried out in conscious lambs (1‐2 weeks old, n= 9) and older sheep (11‐12 weeks old, n= 11) to determine whether the cardiovascular and endocrine responses to 0, 10 and 20% haemorrhage were developmentally regulated. The major novel finding of our study is that throughout the first 3 months of postnatal life, there is a similar decrease in mean arterial pressure and a similar restoration of pressure to pre‐haemorrhage levels, for the same degree of blood loss, yet the mechanisms used to restore pressure appear to be age dependent as follows. In lambs, but not in older sheep, heart rate increased for 1 h after 20% haemorrhage. Activation of the renin‐angiotensin system was also greater and more prolonged in lambs than in older sheep following haemorrhage, and occurred at a lesser degree of blood loss. Plasma arginine vasopressin responses to haemorrhage were, however, similar in both age groups. These data provide new information that some of the mechanisms used to restore arterial pressure following blood volume depletion appear to be age dependent.

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Section: Discussionmentioning

confidence: 87%

Renin and Heart Rate Responses to Haemorrhage are Age Dependent in Conscious Lambs

Smith

Basati

Şener

et al. 2000

Experimental Physiology

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“…Hematocrit was determined in duplicate using a micrometer caliper. RIA, previously established in our laboratory, were used to measure plasma cortisol (22), plasma A11 (25) concentrations, and PRA (25,26).…”

Section: Methodsmentioning

confidence: 99%

Ontogenic Changes and Regulation of Renal Angiotensin II Type 1 Receptor Gene Expression during Fetal and Newborn Life

et al. 1994

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Factors regulating the expression of the angiotensin I1 subtype 1 (AT,) receptor during fetal life have not been investigated previously. The present study was designed 1) to characterize the ontogeny of AT, receptor gene expression in the kidney of fetal and newborn sheep and 2) to determine the influence of both glucocorticoids and renal nerves in modulating AT, gene expression during fetal life and during the transition from fetal to newborn life. We first isolated and cloned a PCR product that has 98 and 94% homology with the cDNA encoding the bovine and pig AT, receptors, respectively, and 99 and 98% homology with the corresponding deduced protein sequences. Probing with this cDNA, we demonstrated that renal AT, mRNA expression did not change significantly during the last trimester of gestation in fetal sheep or immediately after birth but decreased significantly 10 d after birth. We also demonstrated that renal denervation in the fetus had no effect on renal AT, gene expression in 24-h-old newborn lambs. On the other hand, we observed in 130-d twin fetuses that a continuous intraperitoneal infusion (1 mL/h) of cortisol (3 mg/h or 6.2 p,mol/h) for 48 h in one of the twins increased the fetal plasma cortisol concentration from 32.0 + 7.1 to 1126 r 231 nmol/L and produced a significant decrease ( p < 0.005) in renal AT, gene expression compared with the control twin receiving an intraperitoneal infusion of 0.9% NaCl. In summary, this study demonstrates that renal AT, gene expression is elevated during fetal life and decreases after birth. It is also shown that glucocorticoids, but not renal nerves, contribute to the regulation of renal AT, gene expression during development. (Pediatr Res 36: 755-762, 1994)Abbreviations RAS, renin-angiotensin system AII, angiotensin I1 AT,, angiotensin I1 subtype 1 receptor AT,, angiotensin I1 subtype 2 receptor PCR, polymerase chain reaction RSNA, renal sympathetic nerve activity PRA, plasma renin activity rRNA, ribosomal RNA It has become apparent that the physiologic role of the RAS changes during embryonic and fetal maturation (1-4). Early during development, the RAS exerts a major influence o n cellular growth and organ differentiation (3-6). It is only later during fetal life that the RAS becomes an important modulator of blood pressure and distinct A11 receptor subtypes (AT, and AT,) (3, 9, 10). The AT, receptor subtype is expressed early during embryonic life in the rat (11,12), predominates in the fetal mesenchyme (3), and shows a marked decrease in expression during fetal and postnatal maturation (3). On the other hand, the AT, receptor subtype appears later during fetal development in the rat (3, 9, 10) and seems t o b e localized mainly in areas related t o blood pressure regulation and fluid homeostasis (3). Recent studies in rats have also shown that the AT, receptor gene is expressed in the fetal kidney, liver, adrenal, and heart and that the expression of this gene is developmentally regulated (9, lo), in agreement with previous A11 radioligand and in situ rece...

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“…(6). The technique, reliability, and full characterization of this assay in our laboratory have been reported recently (22).…”

Section: Methodsmentioning

confidence: 99%

“…Previous in vitro studies (3, 8, 20,32,33) have shown that the fetal adrenal gland has the ability to synthesize and secrete aldosterone following stimulation by either A-I1 (33), ACTH (33), or increasing potassium concentration (32). More recently, we (2 1, 22) and others (27) demonstrated that in vivo elevation of plasma A-I1 concentration stimulates aldosterone secretion during the last trimester of gestation in fetal lambs but to a lesser degree than in adult ewes (22). However, in vivo attempts to stimulate aldosterone secretion by ACTH (1,5 ) or potassium infusion (3 1) have been unsuccessful, suggesting a relative insensitivity of the fetal adrenal to these stimuli.…”

Section: Abbreviationsmentioning

confidence: 97%

Factors Controlling Aldosterone Secretion during Hypoxemia in Fetal Lambs

Gomez

et al. 1984

Pediatr Res

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SummaryFactors modulating the fetal aldosterone response to hypoxemia were studied in three groups of chronically catheterized fetal lambs between 131 and 143 days of gestation (term, 145 days). One group (control group) received an infusion of 5% dextrose in water; the second group (captopril-treated group) was given captopril, an inhibitor of angiotensin-converting enzyme; the third group (captopril plus dexamethasone-treated group) received dexamethasone in addition to captopril. In all groups of fetuses, hypoxemia was associated with a significant increase in plasma K+ concentration (+0.7 2 0.1 meqtliter). In control fetuses, changes in plasma aldosterone concentration during hypoxemia correlated closely with changes in plasma K+ concentration r = 0.79; P < 0.001) and with changes in plasma angiotensin I1 concentration ( r = 0.77; P < 0.001). In the captopril-treated fetuses, the rise in plasma aldosterone concentration during hypoxemia correlated closely with plasma K+ ( r = 0.79; P < 0.001) but not with plasma angiotensin I1 values ( r = 0.17). No significant correlation was found between percent changes in maternal aldosterone and percent changes in fetal aldosterone during hypoxemia and following recovery ( r = 0.36; P > 0.1) in captopriltreated fetuses. Administration of dexamethasone to fetuses receiving captopril completely inhibited the rise in plasma aldosterone associated with hypoxemia. Taken together, the present results suggest that the rise in plasma aldosterone during hypoxemia is not related to the level of activity of the renin-angiotensin system but depends probably on the increased secretion of adrenocorticotrophin by the fetus. It is also suggested that maternal placental transfer of aldosterone is not an important factor controlling the rise in fetal plasma aldosterone concentration during hypoxemia.Abbreviations A-11, angiotensin I1 ACTH, adrenocorticotrophin PRA, plasma renin activity Much has been learned about the direct mediators governing aldosterone secretion in adult humans and experimental animals ( 14, 18). However, mechanisms regulating aldosterone secretion during fetal life are poorly understood. Previous in vitro studies (3, 8,20,32,33) have shown that the fetal adrenal gland has the ability to synthesize and secrete aldosterone following stimulation by either A-I1 (33), ACTH (33), or increasing potassium concentration (32). More recently, we (2 1, 22) and others (27) demonstrated that in vivo elevation of plasma A-I1 concentration stimulates aldosterone secretion during the last trimester of gestation in fetal lambs but to a lesser degree than in adult ewes (22). However, in vivo attempts to stimulate aldosterone secretion by ACTH (1, 5 ) or potassium infusion (3 1) have been unsuccessful, suggesting a relative insensitivity of the fetal adrenal to these stimuli.On the other hand, we have found a close correlation between plasma aldosterone and plasma potassium concentrations iia nephrectomized fetuses submitted to blood volume depletion (21). Similar findings have also be...

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Comparison of the adrenal and renal responses to angiotensin II fetal lambs and adult sheep.

Cited by 76 publications

References 45 publications

Renin and Heart Rate Responses to Haemorrhage are Age Dependent in Conscious Lambs

Renin and Heart Rate Responses to Haemorrhage are Age Dependent in Conscious Lambs

Ontogenic Changes and Regulation of Renal Angiotensin II Type 1 Receptor Gene Expression during Fetal and Newborn Life

Factors Controlling Aldosterone Secretion during Hypoxemia in Fetal Lambs

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