Comparison of angiotensin II type 1 receptor blockade and angiotensin‐converting enzyme inhibition in pregnant sheep during late gestation

Forhead, Alison J.; Whybrew, Katherine; Hughes, Paul; Pipkin, Fiona Broughton; Sutherland, Mark; Fowden, Abigail L.

doi:10.1111/j.1476-5381.1996.tb15999.x

Cited by 8 publications

(18 citation statements)

References 36 publications

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“…Recent work has demonstrated that administration of GR 1 38950 to pregnant ewes during late gestation causes maternal hypotension and abolishes the maternal pressor response to exogenous All (Forhead et al 1996). These effects occur without influencing basal blood pressure, or the pressor response to All, in the sheep fetus (Forhead et al 1996).…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…These effects occur without influencing basal blood pressure, or the pressor response to All, in the sheep fetus (Forhead et al 1996). GR138950, however, has been detected in the fetal circulation, albeit at low concentrations, within 2 h of maternal administration and is associated with a decrease in fetal oxygenation (Forhead et al 1996). Therefore, antagonism of the AT1 receptor with GR1 38950 in the pregnant ewe also appears to have consequences for the sheep fetus which may be due to direct effects on the fetal RAS or mediated via changes in the maternal circulation.…”

Section: Introductionmentioning

confidence: 99%

“…Measurements were confined to one fetus in the ewes carrying twins. The haemodynamic data obtained from the animals in the current study have been presented in full elsewhere (Forhead et al 1996) and, therefore, are only summarized here.…”

Section: Introductionmentioning

confidence: 99%

“…Maternal ACE inhibition has also been associated with fetotoxicity in a variety of experimental animals, including rabbits, guinea-pigs, baboons and sheep (Broughton Pipkin, Symonds & Turner, 1982; Thomas & Thompson, 1986;Harewood, Phippard, Duggin, Horvath & Tiller, 1994). In sheep, the poor outcome of pregnancy may be due to the hypotension, hypoxaemia and changes in renal function observed in fetuses after maternal treatment with captopril (Lumbers, Kingsford, Menzies & Stevens, 1992;Lumbers, Burrell, Menzies & Stevens, 1993; Whybrew, Hughes, Broughton Pipkin, Sutherland & Fowden, 1996). Since captopril readily crosses the ovine placenta (Stevenson, Gibson & it clear whether these effects seen in the fetus are solely due to direct inhibition of the fetal RAS, or whether they occur secondarily to the changes induced in maternal cardiovascular function and placental perfusion.…”

Section: Introductionmentioning

confidence: 99%

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Changes in the maternal and fetal renin‐angiotensin systems in response to angiotensin II type 1 receptor blockade and angiotensin‐converting enzyme inhibition in pregnant sheep during late gestation

Forhead

Pipkin²,

Sutherland³

et al. 1997

Experimental Physiology

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SUMMARYThe effects of maternal administration of either an angiotensin II type 1 (AT1) receptor antagonist (GR 138950) or an angiotensin-converting enzyme (ACE) inhibitor (captopril) on the renin-angiotensin system (RAS) were investigated in chronically catheterized ewes and their fetuses during late gestation. From 127 + 1 days of gestation until parturition at 145 + 2 days, each ewe received daily I.v. injections of GR138950 (3 mg kg-1, n = 10 animals) or captopril (3 mg kg-1, n = 6) or an equivalent volume of vehicle solution (0.9 % NaCl, n = 10). On the first day of treatment, plasma renin concentrations in the pregnant ewe increased within 2 h of administration of either GR138950 (median change followed by lower and upper quartiles (25 %, 75 %): +38-3 ng ml-' h-1 (15.6, 80.7); P < 0.05) or captopril (+22.1 ng ml-1 h-' (19.2, 28.8); P < 0.05). Maternal plasma concentrations of angiotensin II (All) also increased by 871 pg ml-' (555, 1340; P < 0 05) in the GR138950-treated ewes. In the fetuses of both groups of drug-treated animals, an increase in plasma renin concentration was observed within 2 h of maternal treatment with either GR138950 (+1 1.6 ng ml-' h-' (1.2, 18.6); P < 0 05) or captopril (+59-3 ng ml-' h-' (41.7, 74.6); P < 0.05).These short-term changes in circulating renin and All concentrations observed in the pregnant ewe were sustained after 1 week of GR138950 administration. In addition, 1 week of GR138950 treatment decreased plasma angiotensinogen (Ao) concentrations in both the ewe (-0.36 jug ml-1 (-0 58, -0.16); P < 0.05) and the fetus (-0 43 ,ug ml-1 (-0 59, -0.09); P < 0.05). A long-term reduction in maternal plasma All, and an increase in fetal plasma renin concentration, were associated with I week of captopril administration. Neither drug had any consistent efFect on plasma ACTH or cortisol concentrations in the pregnant ewe or fetus. These findings show that, during ovine pregnancy, antagonism of maternal All activity, either by blockade of the AT1 receptor or by inhibition of All synthesis, induces changes in the circulating components of the RAS in the mother and fetus. In both the pregnant ewe and fetus, the RAS is shown to be activated by suppression of All activity.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Changes in the maternal and fetal renin‐angiotensin systems in response to angiotensin II type 1 receptor blockade and angiotensin‐converting enzyme inhibition in pregnant sheep during late gestation

Forhead

Pipkin²,

Sutherland³

et al. 1997

Experimental Physiology

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Development of the Renin-Angiotensin System

Smith¹

2017

Fetal and Neonatal Physiology

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Outcomes of 83 fetuses exposed to angiotensin receptor blockers during the second or third trimesters: a literature review

et al. 2015

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This literature review was conducted to provide better counsel to pregnant women who erroneously took angiotensin receptor blockers (ARBs) during the second and/or third trimesters regarding infant outcomes. Information was available on 83 fetuses in 34 literature reports, including one that we encountered recently. Fourteen pregnancies were terminated, and six were unknown regarding status of amniotic fluid volume (AFV). Fifty-eight and five fetuses did and did not show oligohydramnios, respectively, after being exposed to ARBs. Of the 58 fetuses that presented with oligohydramnios, 57 were exposed to ARBs at gestational week (GW) ⩾ 20, and 19 exhibited resolution of oligohydramnios 1-6 weeks after cessation of ARBs. The 24 mothers without oligohydramnios at delivery ceased taking ARBs earlier (GW of 26.8 ± 5.1 vs. 31.8 ± 4.0, respectively, P = 0.000) and had longer duration of gestation after cessation of ARBs (8.4 ± 5.2 vs. 0.7 ± 2.3 weeks, respectively, P = 0.000). The mothers without oligohydramnios also had better outcomes in terms of favorable infant outcomes (63% (15/24) vs. 15% (6/39), respectively, P = 0.000) and infant mortality rates (13% (3/24) vs. 56% (22/39), respectively, P = 0.001) than the 39 with oligohydramnios. Thus, a favorable outcome may be feasible if the fetuses are not indicated for prompt delivery at presentation and exhibit normal AFV or resolution of oligohydramnios after cessation of ARBs. Although the prevalence rate of oligohydramnios was high in this study, it may have been due to publication bias. A prospective study suggested a lower prevalence rate than that reported in the present study.

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Comparison of angiotensin II type 1 receptor blockade and angiotensin‐converting enzyme inhibition in pregnant sheep during late gestation

Cited by 8 publications

References 36 publications

Changes in the maternal and fetal renin‐angiotensin systems in response to angiotensin II type 1 receptor blockade and angiotensin‐converting enzyme inhibition in pregnant sheep during late gestation

Changes in the maternal and fetal renin‐angiotensin systems in response to angiotensin II type 1 receptor blockade and angiotensin‐converting enzyme inhibition in pregnant sheep during late gestation

Development of the Renin-Angiotensin System

Outcomes of 83 fetuses exposed to angiotensin receptor blockers during the second or third trimesters: a literature review

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