The effect of chronic nitric oxide inhibition on vascular reactivity and blood pressure in pregnant rats
Keywords:
Vascular reactivity, Pregnancy, Rats; L-NAME, Nitric oxideAbstract
CONTEXT: The exact mechanism involved in changes in blood pressure and peripheral vascular resistance during pregnancy is unknown. OBJECTIVE:To evaluate the importance of endothelium-derivated relaxing factor (EDRF) and its main component, nitric oxide, in blood pressure and vascular reactivity in pregnant rats. DESIGN: Clinical trial in experimentation animals. SETTING: University laboratory of Pharmacology. SAMPLE: Female Wistar rats with normal blood pressure, weight (152 to 227 grams) and age (90 to 116 days). INTERVENTION: The rats were divided in to four groups: pregnant rats treated with L-NAME (13 rats); pregnant control rats (8 rats); virgin rats treated with L-NAME (10 rats); virgin control rats (12 rats). The vascular preparations and caudal blood pressure were obtained at the end of pregnancy, or after the administration of L-NAME in virgin rats. MAIN MEASUREMENTS: The caudal blood pressure and the vascular response to acetylcholine in pre-contracted aortic rings, both with and without endothelium, and the effect of nitric oxide inhibition, Nw-L-nitro-arginine methyl-ester (L-NAME), in pregnant and virgin rats. The L-NAME was administered in the drinking water over a 10-day period. RESULTS: The blood pressure decreased in pregnancy. Aortic rings of pregnant rats were more sensitive to acetylcholine than those of virgin rats. After L-NAME treatment, the blood pressure increased and relaxation was blocked in both groups. The fetal-placental unit weight of the L-NAME group was lower than that of the control group. CONCLUSION: Acetylcholine-induced vasorelaxation sensitivity was greater in pregnant rats and that blood pressure increased after L-NAME administration while the acetylcholine-induced vasorelaxation response was blocked.
Downloads
References
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.