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. 1990 Jun;100(2):341–347. doi: 10.1111/j.1476-5381.1990.tb15806.x

Refractoriness of the gravid rat uterus to tocolytic and biochemical effects of atrial natriuretic peptide.

W Potvin 1, D R Varma 1
PMCID: PMC1917439  PMID: 1974161

Abstract

1. Effects of atrial natriuretic peptide (ANP) on tension development, particulate guanylate cyclase activity and guanosine 3':5'-cyclic monophosphate (cyclic GMP) concentrations of uteri from oestrogen-treated, progesterone-treated, ovariectomized and pregnant rats were determined in vitro. 2. ANP inhibited the tension development by myometrial tissues from oestrogen-treated virgin rats and the sterile horn of 10 to 14 day pregnant rats but not of the uterus from pregnant and progesterone-treated rats. 3. Inhibition of cyclo-oxygenase and lipoxygenase activities did not restore the tocolytic activity of ANP on gravid uterus. ANP exerted a tocolytic effect on nongravid uterus submaximally stimulated by prostaglandin F2 alpha (PGF2 alpha), oxytocin, vasopressin, angiotensin II or 5-hydroxytryptamine (5-HT). 4. Ovariectomy decreased the tocolytic effects of ANP, which could be restored by oestrogen treatment. 5. The refractoriness to the tocolytic effect of ANP in pregnant rats was not accompanied by a decrease in its relaxant effects on isolated aortic strips. 6. Tocolytic effects of isoprenaline, isobutylmethyl xanthine and hydroxylamine were not influenced by pregnancy or progesterone treatment. Up to a concentration of 3 mM, sodium nitroprusside did not affect myometrial tension development. 7. Pregnancy and progesterone treatment markedly inhibited ANP-induced increases in myometrial particulate guanylate cyclase activity and cyclic GMP concentrations but did not influence the effects of ANP on aortic cyclic GMP concentrations. 8. It is concluded that exposure of the myometrium to circulating and placentally-produced progesterone is responsible for the pregnancy-induced decrease in the effects of ANP on myometrial particulate guanylate cyclase activity and cyclic GMP concentrations and in turn on myometrial tension development.

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Selected References

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  1. Beatty C. H., Bocek R. M., Herrington P. T., Young M. K., Brenner R. M. Effects of estradiol-17 beta and progesterone on cyclic nucleotide metabolism in myometrium of macaques. Biol Reprod. 1979 Sep;21(2):309–318. doi: 10.1095/biolreprod21.2.309. [DOI] [PubMed] [Google Scholar]
  2. Bek T., Ottesen B., Fahrenkrug J. The effect of galanin, CGRP and ANP on spontaneous smooth muscle activity of rat uterus. Peptides. 1988 May-Jun;9(3):497–500. doi: 10.1016/0196-9781(88)90154-4. [DOI] [PubMed] [Google Scholar]
  3. Bhalla R. C., Sanborn B. M., Korenman S. G. Hormonal interactions in the uterus: inhibition of isoproterenol-induced accumulation of adenosine 3':5'-cyclic monophosphate by oxytocin and prostaglandins. Proc Natl Acad Sci U S A. 1972 Dec;69(12):3761–3764. doi: 10.1073/pnas.69.12.3761. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cantin M., Genest J. The heart and the atrial natriuretic factor. Endocr Rev. 1985 Spring;6(2):107–127. doi: 10.1210/edrv-6-2-107. [DOI] [PubMed] [Google Scholar]
  5. Castro L. C., Arora C., Parvez S., Parvez H., Valenzuela G., Hobel C. J. Plasma atrial natriuretic peptide levels during the rat estrous cycle, pregnancy, and puerperium. Am J Obstet Gynecol. 1989 Jan;160(1):15–19. doi: 10.1016/0002-9378(89)90078-1. [DOI] [PubMed] [Google Scholar]
  6. Chemtob S., Potvin W., Varma D. R. Selective increase in placental blood flow by atrial natriuretic peptide in hypertensive rats. Am J Obstet Gynecol. 1989 Feb;160(2):477–479. doi: 10.1016/0002-9378(89)90475-4. [DOI] [PubMed] [Google Scholar]
  7. Csapo A. I., Wiest W. G. An examination of the quantitative relationship between progesterone and the maintenance of pregnancy. Endocrinology. 1969 Oct;85(4):735–746. doi: 10.1210/endo-85-4-735. [DOI] [PubMed] [Google Scholar]
  8. Currie M. G., Geller D. M., Cole B. R., Boylan J. G., YuSheng W., Holmberg S. W., Needleman P. Bioactive cardiac substances: potent vasorelaxant activity in mammalian atria. Science. 1983 Jul 1;221(4605):71–73. doi: 10.1126/science.6857267. [DOI] [PubMed] [Google Scholar]
  9. Diamond J. Lack of correlation between cyclic GMP elevation and relaxation of nonvascular smooth muscle by nitroglycerin, nitroprusside, hydroxylamine and sodium azide. J Pharmacol Exp Ther. 1983 May;225(2):422–426. [PubMed] [Google Scholar]
  10. Granger S. E., Hollingsworth M., Weston A. H. A comparison of several calcium antagonists on uterine, vascular and cardiac muscles from the rat. Br J Pharmacol. 1985 May;85(1):255–262. doi: 10.1111/j.1476-5381.1985.tb08854.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Inagami T. Atrial natriuretic factor. J Biol Chem. 1989 Feb 25;264(6):3043–3046. [PubMed] [Google Scholar]
  12. Kuehl F. A., Jr, Ham E. A., Zanetti M. E., Sanford C. H., Nicol S. E., Goldberg N. D. Estrogen-related increases in uterine guanosine 3':5'-cyclic momophosphate levels. Proc Natl Acad Sci U S A. 1974 May;71(5):1866–1870. doi: 10.1073/pnas.71.5.1866. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  14. Laatikainen T. J., Pelkonen J. M., Pesonen A. K. Steroid concentrations in placenta and fetal membranes at elective caesarean section and after spontaneous labour. Placenta. 1982 Jul-Sep;3(3):319–324. doi: 10.1016/s0143-4004(82)80008-8. [DOI] [PubMed] [Google Scholar]
  15. Leiber D., Vesin M. F., Harbon S. Regulation of guanosine 3',5'-cyclic monophosphate levels and contractility in rat myometrium. FEBS Lett. 1978 Feb 15;86(2):183–187. doi: 10.1016/0014-5793(78)80559-6. [DOI] [PubMed] [Google Scholar]
  16. Morishige W. K., Pepe G. J., Rothchild I. Serum luteinizing hormone, prolactin and progesterone levels during pregnancy in the rat. Endocrinology. 1973 May;92(5):1527–1530. doi: 10.1210/endo-92-5-1527. [DOI] [PubMed] [Google Scholar]
  17. Mulay S., Varma D. R. Placental barrier to atrial natriuretic peptide in rats. Can J Physiol Pharmacol. 1989 Jan;67(1):1–4. doi: 10.1139/y89-001. [DOI] [PubMed] [Google Scholar]
  18. Mulay S., Varma D. R., Solomon S. Influence of protein deficiency in rats on hormonal status and cytoplasmic glucocorticoid receptors in maternal and fetal tissues. J Endocrinol. 1982 Oct;95(1):49–58. doi: 10.1677/joe.0.0950049. [DOI] [PubMed] [Google Scholar]
  19. Murad F. Cyclic guanosine monophosphate as a mediator of vasodilation. J Clin Invest. 1986 Jul;78(1):1–5. doi: 10.1172/JCI112536. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Needleman P., Greenwald J. E. Atriopeptin: a cardiac hormone intimately involved in fluid, electrolyte, and blood-pressure homeostasis. N Engl J Med. 1986 Mar 27;314(13):828–834. doi: 10.1056/NEJM198603273141306. [DOI] [PubMed] [Google Scholar]
  21. Olsson K., Karlberg B. E., Eriksson L. Atrial natriuretic peptide in pregnant and lactating goats. Acta Endocrinol (Copenh) 1989 Apr;120(4):519–525. doi: 10.1530/acta.0.1200519. [DOI] [PubMed] [Google Scholar]
  22. Otsuki Y., Okamoto E., Iwata I., Nishino E., Mitsuda N., Mori M., Takagi T., Sugita N., Tanizawa O. Changes in concentration of human atrial natriuretic peptide in normal pregnancy and toxaemia. J Endocrinol. 1987 Aug;114(2):325–328. doi: 10.1677/joe.0.1140325. [DOI] [PubMed] [Google Scholar]
  23. Polacek I., Daniel E. E. Effect of - and -adrenergic stimulation on the uterine motility and adenosine 3'5'-monophosphate level. Can J Physiol Pharmacol. 1971 Nov;49(11):988–998. doi: 10.1139/y71-137. [DOI] [PubMed] [Google Scholar]
  24. Potvin W., Varma D. R. Bronchodilator activity of atrial natriuretic peptide in guinea pigs. Can J Physiol Pharmacol. 1989 Oct;67(10):1213–1218. doi: 10.1139/y89-192. [DOI] [PubMed] [Google Scholar]
  25. Ruzycky A. L., Crankshaw D. J. Role of inositol phospholipid hydrolysis in the initiation of agonist-induced contractions of rat uterus: effects of domination by 17 beta-estradiol and progesterone. Can J Physiol Pharmacol. 1988 Jan;66(1):10–17. doi: 10.1139/y88-002. [DOI] [PubMed] [Google Scholar]
  26. Schirar A., Capponi A., Catt K. J. Regulation of uterine angiotensin II receptors by estrogen and progesterone. Endocrinology. 1980 Jan;106(1):5–12. doi: 10.1210/endo-106-1-5. [DOI] [PubMed] [Google Scholar]
  27. St-Louis J., Parent A., Gutkowska J., Genest J., Schiffrin E. L. Vasorelaxation and vascular binding sites for atrial natriuretic peptide in pregnant rats. Am J Physiol. 1988 Jun;254(6 Pt 2):H1027–H1033. doi: 10.1152/ajpheart.1988.254.6.H1027. [DOI] [PubMed] [Google Scholar]
  28. Thomsen J. K., Storm T. L., Thamsborg G., de Nully M., Bødker B., Skouby S. Atrial natriuretic peptide concentrations in pre-eclampsia. Br Med J (Clin Res Ed) 1987 Jun 13;294(6586):1508–1510. doi: 10.1136/bmj.294.6586.1508. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Tremblay J., Gerzer R., Vinay P., Pang S. C., Béliveau R., Hamet P. The increase of cGMP by atrial natriuretic factor correlates with the distribution of particulate guanylate cyclase. FEBS Lett. 1985 Feb 11;181(1):17–22. doi: 10.1016/0014-5793(85)81105-4. [DOI] [PubMed] [Google Scholar]
  30. Varma D. R., Yue T. L. Adrenoceptor blocking properties of atropine-like agents anisodamine and anisodine on brain and cardiovascular tissues of rats. Br J Pharmacol. 1986 Mar;87(3):587–594. doi: 10.1111/j.1476-5381.1986.tb10201.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Verma S. C., McNeill J. H. Isoproterenol-induced relaxation, phosphorylase activation and cylic adenosine monophosphate levels in the polarized and depolarized rat uterus. J Pharmacol Exp Ther. 1976 Sep;198(3):539–547. [PubMed] [Google Scholar]
  32. Williams L. T., Lefkowitz R. J. Regulation of rabbit myometrial alpha adrenergic receptors by estrogen and progesterone. J Clin Invest. 1977 Oct;60(4):815–818. doi: 10.1172/JCI108835. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Winquist R. J., Faison E. P., Waldman S. A., Schwartz K., Murad F., Rapoport R. M. Atrial natriuretic factor elicits an endothelium-independent relaxation and activates particulate guanylate cyclase in vascular smooth muscle. Proc Natl Acad Sci U S A. 1984 Dec;81(23):7661–7664. doi: 10.1073/pnas.81.23.7661. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. de Bold A. J., Borenstein H. B., Veress A. T., Sonnenberg H. A rapid and potent natriuretic response to intravenous injection of atrial myocardial extract in rats. Life Sci. 1981 Jan 5;28(1):89–94. doi: 10.1016/0024-3205(81)90370-2. [DOI] [PubMed] [Google Scholar]

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