Premium
Comparison of the transplacental transfer of enalapril, captopril and losartan in sheep
Author(s) -
Stevenson Kathleen M.,
Gibson Karen J.,
Lumbers Eugenie R.
Publication year - 1995
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1995.tb13376.x
Subject(s) - enalapril , losartan , enalaprilat , captopril , endocrinology , medicine , transplacental , angiotensin ii , renin–angiotensin system , chemistry , fetus , angiotensin converting enzyme , biology , blood pressure , placenta , pregnancy , genetics
1 The transplacental transfers of three drugs (enalapril, captopril and losartan) which block the renin angiotensin system and have different lipophilicities were studied in chronically catheterized foetal sheep (125–139 days gestation). 2 The ability of the foeto‐placental unit to convert enalapril to enalaprilat was studied in two chronically catheterized foetuses. Enalapril (3 mg kg −1 , 7.9 fimol kg −1 given i.v. to the foetuses abolished the foetal pressor response to 5 μg angiotensin I (AI) in one foetus and attenuated the pressor response in the other. 3 Enalapril (100 mg, 5.7 fimol kg −1 ) given i.v. to the ewe ( n = 5) abolished the maternal pressor response to 2.5 μg AI ( n = 1) and attenuated the maternal pressor response to 5 μg AI ( n = 5, P< 0.001). The foetal pressor response to 5 μg AI ( n = 2) and 10 μg AI ( n = 3) did not change. The maternal and foetal pressor responses to angiotensin II (All; n = 5) did not change. 4 Foetal pressor responses to 5 μg AI ( n = 1) and 10 μg AI ( n = 2) were attenuated within 11 min of their mothers ( n = 3) being given i.v. captopril (15 mg, 1.5 fimol kg‐1). Foetal pressor responses to 5 μg All ( n = 1) and to 10 μg All ( n = 2) did not change. 5 Losartan (10 mg kg −1 , 21.7 fimol kg‐1) given i.v. to the foetus ( n = 9) attenuated the foetal pressor response to 5 μg All (P< 0.001) but the maternal pressor response to 5 μg All did not change. 6 Losartan (100 mg, 21.7 μmol kg‐1) given i.v. to the ewe ( n = 5) attenuated the maternal pressor response to 5 μg All (P< 0.002) but the foetal pressor response to 5 μg All did not change. 7 It is concluded that the foeto‐placental unit of the sheep can metabolize enalapril to enalaprilat. Captopril readily crosses the sheep placenta but enalapril and losartan do not. Thus, the transplacental transfer of these drugs does not parallel their lipid solubilities. Furthermore the results show that AT 1 receptors are important in mediating the vasoconstrictor effects of All in the foetus.