Renin and angiotensin‐like levels in foetal, new‐born and adult sheep

Pipkin, Fiona Broughton; Kirkpatrick, Susan M.; Lumbers, Eugenie R.; Mott, Joan C.

doi:10.1113/jphysiol.1974.sp010672

Cited by 79 publications

(9 citation statements)

References 14 publications

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“…Fetal plasma angiotensin I1 levels have been shown to increase in response to renin (13). Angiotensin I1 levels also have been shown to increase in response to hypoxemia (13) or hemorrhage (12). The hypertensive dose of exogenous angiotensin I1 did not stimulate aldosterone secretion in the three fetal lambs between 117-138 days of gestation.…”

Section: Resultsmentioning

confidence: 97%

Ontogeny of the Renin-Angiotensin-Aldosterone System in the Fetal and Newborn Lamb

Siegel

Fisher

1980

Pediatr Res

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SummaryThirteen chronic fetal lamb preparations between 95 and 142 days of gestation (term 145-150 days), and 10 newborn lambs were studied before and after the acute (1-2 min) infusion of furosemide (2 mg/kg). The baseline to peak plasma renin activity (PRA) response to furosemide increased from A 3.0 & 1.3 ng/ml/hr (M and SEM) and 95-106 days of gestation to A 18.4 +: 4.0 ( P < 0.01) at 123-142 days and A 33.6 + 6.5 (P < 0.001) in the newborn.Baseline plasma aldosterone concentrations were similar in the fetus and pregnant ewe; aldosterone levels were higher in the newborn lamb than in the nonpregnant ewe. The newborn plasma aldosterone response to furosemide via the endogenous reninangiotensin system was A 17.1 2 4.2 ng/dl ( P < 0.01); the fetal lamb plasma aldosterone level did not increase. The results indicate that the renin-angiotensin system cannot be stimulated by furosemide under 106 days of gestation; the response after 110 days increases with gestational age. Aldosterone concentrations in the fetal lamb are probably maintained primarily by the pregnant ewe and do not increase in response to endogenous renin stimulation as in the newborn. SpeculationFetal renin responsiveness increases with gestational age, while fetal aldosterone secretion is unresponsive to stimulation by the renin-angiotensin system. Therefore, the fetal adrenal cortex is the limiting factor in the pituitary-renal-adrenal axis before term.The newborn lamb has high baseline PRA and aldosterone concentrations (15), and the renin-angiotensin-aldosterone system responds promptly to stimulation by furosemide in the newborn lamb. The renin-angiotensin system in the chronic fetal lamb preparation after 110 days of gestation responds to stimulation by furosemide (18) blood volume reduction (13, 17) or aortic constriction (17). Alexander et al. (1) were unable to increase fetal plasma aldosterone levels in three acute fetal sheep preparations by ACTH or exogenous angiotensin I1 infusion and were unable to depress plasma aldosterone with dexamethasone. Although the acute fetal sheep preparation is stressed by surgery, these results suggest that the fetal lamb adrenal gland is unresponsive to aldosterone stimulation or suppression, while the kidney is capable of renin secretion. The present study was conducted to determine in the chronic nonstressed fetal sheep preparation 1) the pattern of baseline PRA and aldosterone levels during the last trimester, and 2) when the system components will respond to stimulation. MATERIALS AND METHODSThirteen chronically catheterized fetal lamb preparations between 95 days of gestation and term and 10 newborn lambs less than 1 wk of age were studied. Pregnant ewes were obtained from a local source and maintained in the vivarium before surgery. Rompun (0.1-0.2 ml), a tranquilizer, was administered to the ewe 9 before uterotomy and fetal catheterization; epidural anesthesia (5 ml of 2% xylocaine) was employed for the surgical procedure. The uterus was exposed through a small midline abdominal incision and the ...

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Section: Resultsmentioning

confidence: 97%

Ontogeny of the Renin-Angiotensin-Aldosterone System in the Fetal and Newborn Lamb

Siegel

Fisher

1980

Pediatr Res

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“…PCR was performed on 1.0 L of RT product with specific primers designed from nucleotide sequences for AT 1 and AT 2 receptors identified from existing sequences in the sheep (synthesized by Life Technologies). Malate dehydrogenase (MDH) was chosen as the reference gene because glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is reported to vary during ovine development (35).…”

Section: Methodsmentioning

confidence: 99%

“…The renin-angiotensin system (RAS) is expressed early in gestation and considered an important modulator of cardiovascular development, adaptation, and blood pressure control before and after birth (1)(2)(3)(4). In fetal and neonatal sheep, hemorrhage and hypovolemia increase circulating angiotensin II (Ang II) (5)(6)(7).…”

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confidence: 99%

Vessel-Specific Regulation of Angiotensin II Receptor Subtypes During Ovine Development

et al. 2005

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Umbilical and systemic responses to angiotensin II differ in term fetal sheep, and peripheral vascular responses are attenuated or absent before and after birth. These observations may reflect developmental differences in angiotensin II receptor (AT) subtypes in vascular smooth muscle (VSM). Studies of AT subtype ontogeny and regulation are generally limited to the aorta, which may not be extrapolated to other arteries, and neither is completely described during ovine development. We therefore characterized VSM AT subtype expression and regulation throughout an extended period of development in umbilical and carotid artery and aorta from fetal (85-146 d gestation), postnatal (5-23 d), and adult sheep, measuring AT 1 and AT 2 mRNA and protein and performing immunohistochemistry. Parallel increases in umbilical AT 1 mRNA and protein began early in gestation and continued to term, and although AT 2 mRNA was unchanged, protein levels decreased Ͼ90% at term. Fetal carotid AT 1 mRNA was Ͻ40% of adult values and unchanged before birth; however, AT 1 protein rose Ͼ2-fold at term. After birth, AT 1 mRNA increased to 85% of adult values and was associated with another 2-fold rise in protein. In contrast, carotid AT 2 mRNA and protein fell in parallel throughout development and were barely detectable in the newborn and the adult. Immunostaining was consistent with observations in both arteries. A third pattern occurred in aortic VSM. The ontogeny of AT subtype expression and regulation is vessel specific, with changes in umbilical VSM beginning very early in development. Although the mechanisms that regulate mRNA and protein expression are unclear, these changes parallel differences in VSM maturation and function and local blood flow. The renin-angiotensin system (RAS) is expressed early in gestation and considered an important modulator of cardiovascular development, adaptation, and blood pressure control before and after birth (1-4). In fetal and neonatal sheep, hemorrhage and hypovolemia increase circulating angiotensin II (Ang II) (5-7). Although inhibition of Ang II receptors (AT) or converting enzyme accentuates hypovolemic episodes (3,7), their effects on basal arterial pressure are inconsistent (8,9). AT blockade also modifies the baroreflex and reflex control of renal sympathetic nerve activity after birth (10,11). Recent evidence suggests the RAS also contributes to the differentiation, maturation, and/or growth of vascular smooth muscle (VSM) (12-15). Thus, prevailing evidence suggests the RAS contributes to the regulation of vascular function, maturation, and growth during development.The effects of the RAS are mediated primarily by Ang II activation of ATs, which belong to the superfamily of seven transmembrane receptors (12,16,17). They are present in mammalian fetal and adult VSM and demonstrate similar binding characteristics during development and in the adult (18 -20). In fetal sheep, AT binding density and affinity in aorta and placental arteries are unchanged in the last third of gestation and resemble ...

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“…The renin-angiotensin-aldosterone (RAA) system has been suggested as a possible regulator of hemodynamic responses to pathophysiological conditions such as hypoxemia (Mattioli et al, 1975;Alward et al, 1978;Robillard et al, 1981). Furthermore, activity of the RAA system varies with postnatal age, including postnatal age-related differences in production of, and response to, angiotensin II, the vasoconstrictor product of angiotensin-converting enzyme activity (Skeggs et al, 1976;Pipkin et al, 1974;Mott, 1975;Siegel and Fisher, 1977;Siegel and Fisher, 1980;Wallace et al, 1980aWallace et al, , 1980bSiegel, 1981).…”

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confidence: 99%

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

Weismann¹,

Herrig²,

McWeeny³

et al. 1983

Circulation Research

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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)

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Renin and angiotensin‐like levels in foetal, new‐born and adult sheep

Cited by 79 publications

References 14 publications

Ontogeny of the Renin-Angiotensin-Aldosterone System in the Fetal and Newborn Lamb

Ontogeny of the Renin-Angiotensin-Aldosterone System in the Fetal and Newborn Lamb

Vessel-Specific Regulation of Angiotensin II Receptor Subtypes During Ovine Development

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

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