The effect of chronic nitric oxide inhibition on vascular reactivity and blood pressure in pregnant rats

Autores

  • Nilton Hideto Takiuti University of São Paulo
  • Maria Helena Cetelli Carvalho University of São Paulo
  • Soubhi Kahhale University of São Paulo
  • Dorothy Nigro University of São Paulo
  • Hermes Vieira Barbeiro University of São Paulo
  • Marcel Zugaib University of São Paulo

Palavras-chave:

Vascular reactivity, Pregnancy, Rats; L-NAME, Nitric oxide

Resumo

CONTEXTO: Os mecanismos envolvidos na diminuição da pressão arterial e da resistência vascular periférica da gravidez não são totalmente esclarecidos, assim como a real importância do fator relaxante derivado do endotélio (Endothelium-derivated relaxing factors - EDRF), um importante modulator do tônus vascular. OBJETIVO: O trabalho avaliou a importância do EDRF e seu principal componente, óxido nitrico, na prenhez das ratas. TIPO DE ESTUDO: Experimentação clínica em animal. LOCAL: Laboratório Universitário de Farmacologia. VARIÁVEIS ESTUDADAS: Foram avaliados, em ratas Wistar normotensas, virgens ou prenhes, a influência da inibição crônica da síntese de óxido nítrico, utilizando o Nw-nitro-L-arginina (L-NAME) diluído na água ingerida pelos animais durante 10 dias e comparadas com os respectivos grupos controles. Foram analisados as repercussões da prenhez e do L-NAME sobre a pressão arterial, reatividade vascular da aorta a acetilcolina in vitro e resultados perinatais. RESULTADOS: A pressão arterial caudal diminui no final da prenhez. A sensibilidade da aorta das ratas prenhes à acetilcolina foi maior que nas virgens. O tratamento com L-NAME determinou aumento da pressão arterial caudal em ambos os grupos de animais e determinou bloqueio no relaxamento induzido pela acetilcolina, de modo semelhante a retirada mecânica do endotélio da aorta. O grupo de ratas prenhes que ingeriram L-NAME apresentou peso da ninhada e do peso de cada feto menor que o grupo controle. CONCLUSÕES: Demonstramos maior sensibilidade para acetilcolina na gestação, contribuindo com a diminuição da pressão arterial e um bloqueio no relaxamento induzido pela acetilcolina após administração de L-NAME.

Downloads

Não há dados estatísticos.

Biografia do Autor

Nilton Hideto Takiuti, University of São Paulo

MD, MSc, Department of Obstetrics and Gynecology, University of São Paulo Medical School and Medical Investigation Laboratory (LIM 57).

Maria Helena Cetelli Carvalho, University of São Paulo

Professor, Pharmacology Department, Biomedical Science Institute of São Paulo University.

Soubhi Kahhale, University of São Paulo

MD and Professor, Department of Obstetrics and Gynecology, University of São Paulo Medical School and Medical Investigation Laboratory (LIM 57).

Dorothy Nigro, University of São Paulo

Professor, Pharmacology Department, Biomedical Science Institute of São Paulo University.

Hermes Vieira Barbeiro, University of São Paulo

Technical assistant, Pharmacology Department, Biomedical Science Institute of São Paulo University, Brazil.

Marcel Zugaib, University of São Paulo

MD, Professor and Chairman, Department of Obstetrics and Gynecology, University of São Paulo Medical School and Medical Investigation Laboratory (LIM 57).

Referências

Wilson M, Morganti AO, Zervoudakis I, et al. Blood pressure, renin-aldosterone system and sex steroids throughout normal pregnancy. Am J Med 1980;68:97-104.

Macgillivray I, Rose GA, Rowe B. Blood pressure surveys in pregnancy. Clin Sci 1969;37:395-8.

Moutquin JM, Rainville C, Giroux L, et al. A prospective study of blood pressure in pregnancy: prediction of pre-eclampsia. Am J Obstet Gynecol 1985;151:91-6.

Kahhale S, Zugaib M. Fisiopatologia da pré-eclâmpsia. In: Síndromes Hipertensivas na Gravidez. 1st ed. Săo Paulo: Atheneu; 1995:15-30.

Walsh SW. Pre-eclampsia: an imbalance in placental prostacyclin and thromboxane production. Am J Obstet Gynecol 1985;152:335-40.

Friedman AF, Taylor NY, Roberts JM. The physiopathology of pre-eclampsia. Clin Perinat 1991;18:661-70.

Furchgott RF, Zawadzki JV. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature 1980;288:373-6.

Furchgott RF. The role of the endothelium response of vascular smooth muscle to drugs. Ann Rev Pharmacol Toxicol 1984;24:175-97.

Furchgott VN, Vanhoutte PM. Endothelium-derivated relaxing and contracting factors. FASEB J 1989;3:2007-18.

Moncada S, Higgs A. The L-arginine-nitric oxide pathway. N Engl J Med 1993;329:2002-12.

Moncada S, Palmer RMJ, Higgs EA. Nitric oxide: physiology, pathophysiology and pharmacology. Pharmacol Rev 1991;43:109-42.

Waldman SA, Murad F. Biochemical mechanism underlying vascular smooth muscle relaxation: the guanylate cyclase-cyclic GMP system. J Cardiovasc Pharmacol 1988;12(5):S115-8.

Palmer RMJ, Moncada S. A novel citrulline-forming enzyme implicated in the formation of nitric oxide by vascular endothelial cells. Biochem Biophys Res Commun 1989;158:348-52.

Palmer RMJ, Rees DD, Ashton DS, Moncada S. L-arginine is the physiological precursor for the formation of nitric oxide in endothelial-dependent relaxation. Biochem Biophys Res Commun 1988;153:1251-6.

Nathan L, Cuevas J, Chaudhuri G. The role of nitric oxide in the altered vascular reactivity of pregnancy in the rat. Br J Pharmacol 1995;114:955-60.

Ahokas RA, Sibai BM. Endothelium-derivated relaxing factors inhibition augments vascular angiotensin-II reactivity in the pregnant rat hind limb. Am J Obstet Gynecol 1992;167:1053-8.

Allen R, Castro L, Arora C, et al. Endothelium-derivated relaxing factor inhibition and the pressor response to norepinephine in the pregnant rat. Obstet Gynecol 1994;83:92-6.

Whelton A, Watson AJ, Rock RC. Nitrogen metabolites and renal function. In: Burtis CA, Ashwood ER, editors. Tietz Textbook of Clinical Chemistry. 2nd ed. Philadelphia: Saunders; 1994:1536-9.

Molnar M, Hertelendy F. Nw-nitro-L-arginine, an inhibitor of nitric oxide synthesis, increases blood pressure in rats and reverses the pregnancy-induced refractoriness to vasopressor agents. Am J Obstet Gynecol 1992;166:1560-7.

Chu ZM, Beilin LJ. Mechanisms of vasodilatation in pregnancy: studies of the role of prostaglandins and nitric oxide in changes of vascular reactivity in the in situ blood-perfused mesentery of pregnant rats. Br J Pharmacol 1993;109:322-9.

Aoi W, Gable D, Cleary RE, Young PCM, Weinberger MH. The antihypertensive effect of pregnancy in spontaneously hypertensive rats. Proc Soc Exp Biol Med 1976;153:13-5.

Baylis C, Davinson J. The Urinary System. In: Hytten F, Chamberleined G, editors. Clinical Physiology in Obstetrics. Oxford: Blackwell Scientific 1990:245-302.

Baylis C, Engels K. Adverse interactions between pregnancy and the new model of systemic hypertension produced by chronic blockade of endothelium-derivated relaxing factor (EDRF) in rats. Clin Exper Hyper Pregnancy 1992; b(11):117-29.

Ahokas RA, Mercer BM, Sibai BM. Enhanced endothelium-derivated relaxing factor activity in pregnant spontaneously hypertensive rats. Am J Obstet Gynecol 1991;165:801-7.

Lindheimer MD, Katz AI, Koeppen BM, Ordonez NG, Oparil S. Kidney function and sodium handling in the pregnant spontaneously hypertensive rat. Hypertension 1983;5:498-506.

Ljungblad U, Karlsson K, Lundgren Y. The effect of pregnancy on heart size and blood pressure in renal hypertensive rats. Clin Exper Hyper pregnancy 1983;b2:61-74.

St-Louis J, Sciotte B. Prostaglandin- or endothelium-mediated vasodilatation is not involved in the blunted response of blood vessels to vasoconstrictors in pregnant rats. Am J Obstet Gynecol 1992;166:684-92.

Takeda T. Experimental study on the blood pressure of pregnant hypertensive rats: I: Effects of pregnancy on the course of experimentally and spontaneously hypertensive rats. Jap Circulation J 1964;28:49-54.

Paller MS. Mechanism of decreased pressor responsiveness to angiotensin II, norepinefrine and vasopressine in pregnant rats. Am J Physiol 1984;247:H100-8.

Conrad KP. Renal hemodynamics during pregnancy in chronically catheterized, conscious rats. Kidney Int 1984;26:24-9.

Blizzard DA, Folk TG. Resource-sharing in rat gestation: role of maternal cardiovascular hemodynamics. Am J Physiol 1990;250:R1299-307.

Metcalfe J, Stock MK, Barron DH. Maternal physiology during gestation. In: Knobil E, Neil JD, Ewing LL, et al. The Physiology of reproduction. New York: Raven Press;1988:2145-76.

Weiner C, Martinez E, Zhu LK, Ghodsi A, Chesnut D. In vitro release of endothelium-derivated relaxing factor by acetylcholine is increased during the guinea pig pregnancy. Am J Obstet Gynecol 1989;161:1599-605.

Feletou M, Vanhoutte PM. Endothelium-dependent hyperpolarization of canine coronary smooth muscle. Br J Pharmacol 1988;93:515-24.

Yallampalli C, Garfield RE. Inhibition of nitric oxide synthesis in rats during pregnancy produces signs similar to those of pre-eclampsia. Am J Obstet Gynecol 1993;169:1316-20.

Downloads

Publicado

1999-09-09

Como Citar

1.
Takiuti NH, Carvalho MHC, Kahhale S, Nigro D, Barbeiro HV, Zugaib M. The effect of chronic nitric oxide inhibition on vascular reactivity and blood pressure in pregnant rats. Sao Paulo Med J [Internet]. 9º de setembro de 1999 [citado 16º de outubro de 2025];117(5):197-204. Disponível em: https://periodicosapm.emnuvens.com.br/spmj/article/view/2585

Edição

Seção

Artigo Original