Selective Vasodilator Effects of Atrial Natriuretic Peptide in the Human Placental Vasculature

Abstract

Objective: To determine whether atrial natriuretic peptide (ANP) attenuates the vasocon-strictor effects of angiotensin II (AII), a thromboxane mimetic (U46619), and endothelin-1 in the human fetal-placental vasculature and to determine whether nitric oxide (NO) has a role in the vasodilator activity of ANP.

Methods: Isolated placental cotyledons were dually perfused, with fetal perfusion pressure used as an index of vascular response. The effects of AII (10^-10-10^-6 mol/L bolus injection), endothelin-1 (10^-7 mol/L bolus), and U46619 (10^-9-10^-6 mol/L bolus or 10^-8 mol/L infusion) were established in the absence or presence of ANP (10^-8 mol/L). The role of NO as a mediator of ANP action was investigated by perfusion with n-nitro-L-arginine (NNLA, 10^-3 mol/L), an inhibitor of NO synthase. Statistical significance was determined by analysis of variance.

Results: Atrial nutriuretic peptide caused significant attenuation of vasoconstrictor responses to AII, but weak attenuation of endothelin-1 and no attenuation of U46619. Use of NNLA did not affect the attenuation of AII-induced vasoconstriction by ANP.

Conclusion: Atrial natriuretic peptide is a vasodilator of the fetal-placental vasculature constricted with AII and endothelin-1, but not with U46619. Nitric oxide does not mediate the action of ANP.

Keywords

Atrial natriuretic peptide placenta nitric oxide angiotensin thromboxane mimetic endothelin-1

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References

1. Myatt L . Current topic: Control of vascular resistance in the human placenta. Placenta 1992;13:329-341.

2. Gardner DG , Hedges BK , Wu J , LaPointe MC , Deschepper CF . Expression of atrial natriuretic peptide gene in human fetal heart. J Clin Endocrinol Metab 1989;69:729-737.

3. Gardner DG , Vlasuk GP , Baxter JD , Fiddes JC , Lewicki JA . Identification of atrial natriuretic factor transcripts in the central nervous system of the rat. Proc Natl Acad Sci USA 1987;84:2175-2179.

4. Gardner DG , Deschepper CF , Ganong W , et al. Extra-atrial expression of the gene for atrial natriuretic factor. Proc Natl Acad Sci USA 1986;83:6697-6701.

5. Morel G , Chabot J-G , Garcia-Caballero T , et al. Synthesis, internalization and localization of atrial natriuretic peptide in rat adrenal medulla. Endocinology 1988;123:149-158.

6. Robillard JE , Weiner CP . Atrial natriuretic factor in the human fetus: Effect of volume expansion. J Radiat 1988;113:552-555.

7. Fisk NM , Tannirandorn Y , Nicolini U , Hubinont C , Rodeck CH . Atrial natriuretic peptide in fetal disease. Br J Obstet Gynaecol 1990;97:545-546.

8. Panos MZ , Nicolaides KH , Anderson IV , Economides PL , Rees L , Williams R . Plasma atrial natriuretic peptide in human fetus: Response to intravascular blood transfusion. Am J Obstet Gynecol 1989;161:357-361.

9. Robillard JE , Nakamura KT , Varille VA , Anderson AA , Matherne GP , VanOrden DE . Ontogeny of the renal response to natriuretic peptide in sheep. Am J Physiol 1988;254(Renal Fluid Electrolyte Physiology 23):F634-F641.

10.

10. Saavedra IM , Correa FM , Plunkett LM , Israel A , Kurihara M , Shigematsu K . Binding of angiotensin and atrial natriuretic peptide in brain of hypertensive rat. Nature 1986;320:758-760.

11.

11. McQueen J , Kingdom JC , Whittle MJ , Connell JM . Characterization of atrial natriuretic peptide receptors in human fetoplacental vasculature. Am J Physiol 1993;264:H798-H804.

12.

12. McQueen J , Jardine AG , Kingdom JCP , Templetone A , Whittle MJ , Connell JMC . Interaction of angiotensin II and atrial natriuretic peptide in the human fetoplacental unit. Am J Hypertens 1990;3:641-649.

13.

13. Gerzer R , Heim J-M , Schutte B , Weil J . Cellular mechanisms of action of atrial natriuretic factor. Klin Wochenschr 1987;8(Suppl 65):109-114.

14.

14. Anand-Srivastava MB , Sairam MR , Cantin M . Ring-deleted analogs of atrial natriuretic factor inhibit adenylate cyclase/cAMP system. J Biol Chem 1990;265:8566-8572.

15.

15. Lincoln TM , Cornwell TL . Intracellular cyclic GMP receptor proteins. FASEB J 1993;7:328-338.

16.

16. Frost SJ , Whitson PA . Characterization of atrial natriuretic peptide degradation by cell-surface peptidase activity on endothelial cells. J Cell Biochem 1993;52:227-236.

17.

17. Glance DG , Elder MG , Myatt L . The action of prostaglandins and their interactions with angiotensin II in isolated perfused human placental cotyledon. Br J Obstet Gynaecol 1986;93:488-494.

18.

18. Myatt L , Langdon G , Brewer AS , Brockman DE . Endothelin-1-induced vasoconstriction is not mediated by thromboxane release and action in the human fetal-placental circulation. Am J Obstet Gynecol 1991;165:1717-1722.

19.

19. Myatt L , Brewer AS , Langdon G , Brockman DE . Attenuation of the vasoconstrictor effects of thromboxane and endothelin by nitric oxide in the human fetal-placental circulation. Am J Obstet Gynecol 1992;166:224-230.

20.

20. Gardner DG , Newman ED , Nakamura KK , Nguyen KPT . Endothelin increases the synthesis and secretion of atrial natriuretic peptide in neonatal rat cardiocytes. Am J Physiol 1991;261(Endocrinol Metab 24):E177-E182.

21.

21. Gruetter CA , Barry BK , McNamara DB , Gruetter DY , Kadowitz PJ , Ignarro LJ . Relaxation of bovine coronary artery and activation of coronary atrial guanylate cyclase by nitric oxide, nitroprusside and a carcinogenic nitrosamine. J Cyclic Nucleotide Protein Phosphorylation Res 1979;5:211-214.

22.

22. Matsumoto T , Okamura T , Kinoshita M , Toda N . Interaction of nitrovasodilators and atrial natriuretic peptide in isolated dog coronary arteries. Eur J Pharmacol 1993;237:31-37.

23.

23. Glance DG , Bloxam DL , Elder MG , Myatt L . The effects of the components of the renin-angiotensin system on the isolated perfused human placental cotyledon. Am J Obstet Gynecol 1984;149:450-454.

24.

24. Imura H , Nakao K , Itoh H . The natriuretic peptide system in the brain: Implications in the central control of cardiovascular and neuroendocrine functions. Front Neuroendocrinol 1992;13:217-219.

25.

25. Inagami T . Atrial natriuretic factor. J Biol Chem 1989;264:3043-3046.

26.

26. Brace RA , Bayer LA , Cheung CY . Fetal cardiovascular, endocrine, and fluid responses to atrial natriuretic factor infusion. Am J Physiol 1989;257(Regulatory integrative Comp Physiol 26):R580-R587.

27.

27. Kingdom JCP , Ryan G , Whittle MJ , et al. Atrial natriuretic peptide: A vasodilator of the placental circulation? Am J Obstet Gynecol 1991;165:791-800.

28.

28. McQueen J , Kingdom JCP , Jardine AG , Connell JMC , Whittle MJ . Vascular angiotensin II and atrial natriuretic peptide receptors in normal and growth-retarded human placentae. J Endocrinol 1990;126:341-347.

29.

29. Weir RI , Brown II , Fraser R . Relationship between plasma renin, renin-substrate and angiotensin II, aldosterone and electrolytes in normal pregnancy. J Clin Endocrinol Metab 1975;40:108-115.

30.

30. Gant NF , Daley GL , Chand S , Whalley PJ , McDonald PC . A study of angiotensin II receptor response throughout primigravid pregnancy. J Clin Invest 1973;52:2682-2689.

31.

31. Rosenfeld CR , Samson WK , Roy TA , Faucher DJ , Magness RR . Vasoconstrictor-induced secretion of ANP in fetal sheep. Am J Physiol 1992;263:E526-E533.

32.

32. Holcberg G , Kossenjans W , Brewer A , Miodovnik M , Myatt L . The action of two natriuretic peptides (ANP and BNP) in the human placental vasculature. Am J Obstet Gynecol (in press).

33.

33. Atlas SA , Laragh JH . Atrial natriuretic peptide: A new factor in hormonal control of blood pressure and electrolyte homeostasis. Annu Rev Med 1986;37:397-414.