Abstract
1. Renal function was studied in chronically catheterized fetal sheep (119-128 days gestation), before and during treatment of the ewe with the angiotensin converting enzyme (ACE) inhibitor, captopril, which crosses the placenta and blocks the fetal renin angiotensin system. 2. An i.v. dose of 15 mg (about 319 micrograms kg-1) of captopril to salt-replete ewes followed by an infusion to the ewe of 6 mg h-1 (about 128 micrograms kg-1 h-1) caused a fall in fetal arterial pressure (P < 0.01), and a rise in fetal renal blood flow (RBF) from 67.9 +/- 5.6 to 84.9 +/- 8.3 ml min-1 (mean +/- s.e. mean) (P < 0.05). Renal vascular resistance and glomerular filtration rate (GFR) fell (P < 0.01); fetal urine flow (P < 0.01); fetal urine flow (P < 0.01) and sodium excretion declined (P < 0.05). 3. Ewes were treated for the next 2 days with 15 mg captopril twice daily. On the 4th day, 15 mg was given to the ewe and fetal renal function studied for 2 h during the infusion of captopril (6 mg h-1) to the ewe. Of the 9 surviving fetuses, 3 were anuric and 3 had low urine flow rates. When 6 micrograms kg-1 h-1 of angiotensin II was infused directly into the fetus RBF fell from 69 +/- 10.1 ml min-1 to 31 +/- 13.9 ml min-1, GFR rose (P < 0.05) and urine flow (P < 0.01) and sodium excretion increased in all fetuses.(ABSTRACT TRUNCATED AT 250 WORDS)
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Selected References
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- Anderson W. P., Denton K. M., Woods R. L., Alcorn D. Angiotensin II and the maintenance of GFR and renal blood flow during renal artery narrowing. Kidney Int Suppl. 1990 Nov;30:S109–S113. [PubMed] [Google Scholar]
- Armentrout T., Katz S., Thornburg K. L., Faber J. J. Osmotic flow through the placental barrier of chronically prepared sheep. Am J Physiol. 1977 Oct;233(4):H466–H474. doi: 10.1152/ajpheart.1977.233.4.H466. [DOI] [PubMed] [Google Scholar]
- Brent R. L., Beckman D. A. Angiotensin-converting enzyme inhibitors, an embryopathic class of drugs with unique properties: information for clinical teratology counselors. Teratology. 1991 Jun;43(6):543–546. doi: 10.1002/tera.1420430602. [DOI] [PubMed] [Google Scholar]
- Broughton Pipkin F., O'Brien P. M. Effect of the specific angiotensin antagonist (Sar1) (Ala8) angiotensin II on blood pressure and the renin-angiotensin system in the conscious pregnant ewe and fetus. Am J Obstet Gynecol. 1978 Sep 1;132(1):7–15. doi: 10.1016/0002-9378(78)90790-1. [DOI] [PubMed] [Google Scholar]
- Broughton Pipkin F., Symonds E. M., Turner S. R. The effect of captopril (SQ14,225) upon mother and fetus in the chronically cannulated ewe and in the pregnant rabbit. J Physiol. 1982 Feb;323:415–422. doi: 10.1113/jphysiol.1982.sp014081. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Caine A. C., Lumbers E. R., Reid I. A. The effects and interactions of angiotensin and vasopressin on the heart of unanaesthetized sheep. J Physiol. 1985 Oct;367:1–11. doi: 10.1113/jphysiol.1985.sp015810. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Elbourne I., Lumbers E. R., Hill K. J. The secretion of organic acids and bases by the ovine fetal kidney. Exp Physiol. 1990 Mar;75(2):211–221. doi: 10.1113/expphysiol.1990.sp003395. [DOI] [PubMed] [Google Scholar]
- Gibson K. J., Lumbers E. R. Mechanisms by which the pregnant ewe can sustain increased salt and water supply to the fetus. J Physiol. 1992 Jan;445:569–579. doi: 10.1113/jphysiol.1992.sp018940. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Györy A. Z., Edwards K. D. Simultaneous titrimetric determination of bicarbonate and titratable acid of urine. Aust J Exp Biol Med Sci. 1967 Apr;45(2):141–147. doi: 10.1038/icb.1967.11. [DOI] [PubMed] [Google Scholar]
- Györy A. Z., Edwards K. D., Stewart J. H., Whyte H. M. Comprehensive one-day renal function testing in man. J Clin Pathol. 1974 May;27(5):382–391. doi: 10.1136/jcp.27.5.382. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hall J. E., Coleman T. G., Guyton A. C., Balfe J. W., Salgado H. C. Intrarenal role of angiotensin II and [des-Asp1]angiotensin II. Am J Physiol. 1979 Mar;236(3):F252–F259. doi: 10.1152/ajprenal.1979.236.3.F252. [DOI] [PubMed] [Google Scholar]
- Hanssens M., Keirse M. J., Vankelecom F., Van Assche F. A. Fetal and neonatal effects of treatment with angiotensin-converting enzyme inhibitors in pregnancy. Obstet Gynecol. 1991 Jul;78(1):128–135. [PubMed] [Google Scholar]
- Heymann M. A., Payne B. D., Hoffman J. I., Rudolph A. M. Blood flow measurements with radionuclide-labeled particles. Prog Cardiovasc Dis. 1977 Jul-Aug;20(1):55–79. doi: 10.1016/s0033-0620(77)80005-4. [DOI] [PubMed] [Google Scholar]
- Hill K. J., Lumbers E. R. Renal function in adult and fetal sheep. J Dev Physiol. 1988 Apr;10(2):149–159. [PubMed] [Google Scholar]
- Iwamoto H. S., Rudolph A. M. Effects of endogenous angiotensin II on the fetal circulation. J Dev Physiol. 1979 Aug;1(4):283–293. [PubMed] [Google Scholar]
- Kleinman L. I., Lubbe R. J. Factors affecting the maturation of glomerular filtration rate and renal plasma flow in the new-born dog. J Physiol. 1972 Jun;223(2):395–409. doi: 10.1113/jphysiol.1972.sp009854. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lumbers E. R., Hill K. J., Bennett V. J. Proximal and distal tubular activity in chronically catheterized fetal sheep compared with the adult. Can J Physiol Pharmacol. 1988 Jun;66(6):697–702. doi: 10.1139/y88-111. [DOI] [PubMed] [Google Scholar]
- Lumbers E. R., Kingsford N. M., Menzies R. I., Stevens A. D. Acute effects of captopril, an angiotensin-converting enzyme inhibitor, on the pregnant ewe and fetus. Am J Physiol. 1992 May;262(5 Pt 2):R754–R760. doi: 10.1152/ajpregu.1992.262.5.R754. [DOI] [PubMed] [Google Scholar]
- Lumbers E. R., Lewes J. L. The actions of vasoactive drugs on fetal and maternal plasma renin activity. Biol Neonate. 1979;35(1-2):23–32. doi: 10.1159/000241150. [DOI] [PubMed] [Google Scholar]
- Lumbers E. R., Smith F. G., Stevens A. D. Measurement of net transplacental transfer of fluid to the fetal sheep. J Physiol. 1985 Jul;364:289–299. doi: 10.1113/jphysiol.1985.sp015745. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lumbers E. R., Stevens A. D. Changes in fetal renal function in response to infusions of a hyperosmotic solution of mannitol to the ewe. J Physiol. 1983 Oct;343:439–446. doi: 10.1113/jphysiol.1983.sp014902. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lumbers E. R., Stevens A. D. The effects of frusemide, saralasin and hypotension on fetal plasma renin activity and on fetal renal function. J Physiol. 1987 Dec;393:479–490. doi: 10.1113/jphysiol.1987.sp016834. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Robillard J. E., Gomez R. A., VanOrden D., Smith F. G., Jr Comparison of the adrenal and renal responses to angiotensin II fetal lambs and adult sheep. Circ Res. 1982 Jan;50(1):140–147. doi: 10.1161/01.res.50.1.140. [DOI] [PubMed] [Google Scholar]
- Robillard J. E., Weismann D. N., Gomez R. A., Ayres N. A., Lawton W. J., VanOrden D. E. Renal and adrenal responses to converting-enzyme inhibition in fetal and newborn life. Am J Physiol. 1983 Feb;244(2):R249–R256. doi: 10.1152/ajpregu.1983.244.2.R249. [DOI] [PubMed] [Google Scholar]
- Robillard J. E., Weismann D. N., Herin P. Ontogeny of single glomerular perfusion rate in fetal and newborn lambs. Pediatr Res. 1981 Sep;15(9):1248–1255. doi: 10.1203/00006450-198109000-00005. [DOI] [PubMed] [Google Scholar]
- Schubiger G., Flury G., Nussberger J. Enalapril for pregnancy-induced hypertension: acute renal failure in a neonate. Ann Intern Med. 1988 Feb;108(2):215–216. doi: 10.7326/0003-4819-108-2-215. [DOI] [PubMed] [Google Scholar]
- Tack E. D., Perlman J. M. Renal failure in sick hypertensive premature infants receiving captopril therapy. J Pediatr. 1988 May;112(5):805–810. doi: 10.1016/s0022-3476(88)83213-x. [DOI] [PubMed] [Google Scholar]
- Thomsen K., Holstein-Rathlou N. H., Leyssac P. P. Comparison of three measures of proximal tubular reabsorption: lithium clearance, occlusion time, and micropuncture. Am J Physiol. 1981 Oct;241(4):F348–F355. doi: 10.1152/ajprenal.1981.241.4.F348. [DOI] [PubMed] [Google Scholar]
