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Effects of estrogen on nitric oxide biosynthesis and vasorelaxant activity in sheep uterine and renal arteries in vitro

      Abstract

      OBJECTIVES: Our purpose was to determine whether estrogen alters the relaxation responses to bradykinin and superoxide dismutase of the uterine and renal arteries and to determine the role of nitric oxide in that response. STUDY DESIGN: Ten nulliparous, ovariectomized nonpregnant sheep received either estradiol-17β or vehicle solution. In vitro studies evaluating vasorelaxation were done with either bradykinin or superoxide dismutase. The nitric oxide inhibitor Nω-nitro-L-arginine methyl ester was used to determine the role of nitric oxide in this process. Nitric oxide synthase activity was assessed by measuring citrulline generation. RESULTS: We found a dose dependency of relaxation to bradykinin and superoxide dismutase. Estrogen enhanced this response in uterine arteries. Estrogen increased citrulline generation in uterine but not renal arteries. Nω-nitro-L-arginine methyl ester blocked relaxation responses and citrulline generation in both arteries. CONCLUSION: In nonpregnant sheep we found that nitric oxide release and nitric oxide synthase activity is enhanced by estrogen in the uterine arteries but not in the renal arteries. Increases in nitric oxide synthase activity may be important in the hyperemic response of the uterus during estrus. (AM J OBSTET GYNECOL 1996;174:1043-9.)

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      References

        • Magness RR
        • Parker Jr, CR
        • Rosenfeld CR
        Systemic and uterine responses to chronic infusion of estradiol-17β.
        Am J Physiol. 1993; 265: E690-E698
        • Naden RP
        • Rosenfeld CR
        Systemic and uterine responsiveness to angiotensin II and norepinephrine in estrogen-treated nonpregnant sheep.
        AM J OBSTET GYNECOL. 1985; 153: 417-425
        • Furchgott RF
        • Zawadzki JV
        The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine.
        Nature. 1980; 288: 373-376
        • Toda N
        Acetylcholine-induced relaxation in isolated dog cerebral arteries.
        J Pharmacol Exp Ther. 1979; 209: 352-358
        • Vane JR
        • Anggard EE
        • Botting R
        Regulatory functions of the vascular endothelium.
        N Engl J Med. 1990; 323: 27-36
        • Van Buren GA
        • Yang DS
        • Clark K
        Estrogen-induced uterine vasodilatation is antagonized by L-nitroarginine methyl ester, an inhibitor of nitric oxide synthesis.
        AM J OBSTET GYNECOL. 1992; 167: 828-833
        • Rosenfeld CR
        • Moriss FH
        • Battaglia FC
        • Makowski EL
        • Meschia G
        Effect of estradiol-17β on blood flow to reproductive and nonreproductive tissues in pregnant ewes.
        AM J OBSTET GYNECOL. 1976; 124: 618-629
        • Li P
        • Tong C
        • Eisenach JC
        • Figueroa JP
        NDMA causes release on nitric oxide from rat spinal cord in vitro.
        Brain Res. 1994; 637: 287-291
        • Bradford MM
        A rapid and sensitive method for the quantification of microgram quantities of protein utilizing the principle of protein-dye binding.
        Ann Biochem. 1976; 72: 248-254
        • Collins P
        • Shay J
        • Jiang C
        • Moss J
        Nitric oxide accounts for dose-dependent estrogen-mediated coronary relaxation after acute estrogen withdrawal.
        Circulation. 1994; 90: 1964-1968
        • Förstermann U
        • Closs EI
        • Pollock JS
        • et al.
        Nitric oxide synthase isoenzymes characterization, purification, molecular cloning, and functions.
        Hypertension. 1994; 23: 1121-1131
        • Randall NJ
        • Beard RW
        • Sutherland IA
        • Figueroa JP
        • Drost CJ
        • Nathanielsz PW
        Validation of thermal techniques for measurement of pelvic organ blood flows in the nonpregnant sheep: comparison with transit-time ultrasonic and microsphere measurements of blood flow.
        AM J OBSTET GYNECOL. 1988; 158: 651-658
        • Rosenfeld CR
        Distribution of cardiac output in ovine pregnancy.
        Am J Physiol. 1977; 232: H231-H235
        • Kim TH
        • Weiner CP
        • Thompson LP
        Effect of pregnancy on contraction and endothelium-mediated relaxation of renal and mesenteric arteries.
        Am J Physiol. 1994; 267: H41-H47
        • Weiner CP
        • Lizasoain I
        • Baylis SA
        • Knowles RG
        • Charles IG
        • Moncada S
        Induction of calcium-dependent nitric oxide synthases by sex hormones.
        Proc Natl Acad Sci U S A. 1994; 91: 5212-5216
        • Briner VA
        • Tsai P
        • Schrier RW
        Bradykinin: potential for vascular constriction in the presence of endothelial injury.
        Am J Physiol. 1993; 264: F322-F327
        • Naess PA
        • Kirkebøen KA
        • Christensen G
        • Kiil F
        Inhibition of renal nitric oxide synthesis with NG-monomethyl-L-arginine and NG-nitro-L-arginine.
        Am J Physiol. 1992; 262: F939-F942
        • Rees DD
        • Palmer RMJ
        • Hodson HF
        • Moncada S
        A specific inhibitor of nitric oxide formation from L-arginine attenuates endothelium-dependent relaxation.
        Br J Pharmacol. 1989; 96: 418-424
        • Miller VM
        • Vanhoutte PM
        17β-Estradiol augments endothelium-dependent contractions to arachidonic acid in rabbit aorta.
        Am J Physiol. 1990; 258: R1502-R1507
        • Feletou M
        • Vanhoutte PM
        Endothelium-dependent hyperpolarization of the canine coronary artery smooth muscle.
        Br J Pharmacol. 1988; 93: 515-524
        • Leroy DC
        • Crake T
        • Uren NG
        • Davies GJ
        • Maseri A
        Effects of nitric oxide in the human coronary circulation.
        Circulation. 1993; 88: 43-54
        • Venema RC
        • Nishida K
        • Alexander RW
        • Harrison DG
        • Murphy TJ
        Organization of the bovine gene encoding the endothelial nitric oxide synthase.
        Biochem Biophys Acta. 1994; 1218: 413-420
        • Marsden PA
        • Schappert KT
        • Chen HS
        • et al.
        Molecular cloning and characterization of human endothelial nitric oxide synthase gene.
        FEBS Lett. 1992; 307: 287-293
        • Janssens SP
        • Shimouchi A
        • Quertermous T
        • Bloch KD
        Cloning and expression of a cDNA encoding human endothelium-derived relaxing factor/nitric oxide synthase.
        J Biol Chem. 1992; 267: 14519-14522
        • Hishikawa K
        • Nakaki T
        • Marumo T
        • Suzuki H
        • Kato R
        • Saruta T
        Up-regulation of nitric oxide synthase by estradiol in human aortic endothelial cells.
        FEBS Lett. 1995; 360: 291-293
        • Cooke JP
        • Rossitch E
        • Andon NA
        • Loscalzo J
        • Dzau VJ
        Flow activates an endothelial potassium channel to release an endogenous nitrovasodilator.
        J Clin Invest. 1991; 88: 1663-1671
        • Hecker M
        • Muelsch A
        • Bassenge E
        • Förstermann U
        • Busse R
        Subcellular localization and characterization of nitric oxide synthase(s) in endothelial cells: physiological implications.
        Biochemistry. 1994; 299: 247-252
        • Kuchan MJ
        • Jo H
        • Frangos JA
        Role of G proteins in shear stress-mediated nitric oxide production by endothelial cells.
        Am J Physiol. 1994; 267: C753-C758
        • Kamini A
        • Togawa T
        Adaptive regulation of wall shear stress to flow change in the canine carotid artery.
        Am J Physiol. 1980; 239: H14-H21
        • Griffith TM
        • Edwards DH
        • Davies RL
        • Henderson AH
        The role of EDRF in flow distribution: a microangiographic study of the rabbit isolated ear.
        Microvasc Res. 1989; 37: 162-177
        • Joannides R
        • Haefeli WE
        • Linder L
        • et al.
        Nitric oxide is responsible for flow-dependent dilatation of human peripheral conduit arteries in vivo.
        Circulation. 1995; 91: 1314-1319
        • Welch WJ
        • Wilcox CS
        • Aisaka K
        • et al.
        Nitric oxide synthesis from L-arginine modulates renal vascular resistance in isolated perfused and intact rat kidneys.
        J Cardiovasc Pharmacol. 1991; 17: S165-S168
        • Weiner CP
        • Knowles RC
        • Moncada S
        Induction of nitric oxide synthases early in pregnancy.
        AM J OBSTET GYNECOL. 1994; 171: 838-843