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The effect of chronic nitric oxide synthesis inhibition on blood pressure and angiotensin II responsiveness in the pregnant rat.
Am J Obstet Gynecol. 1997 May; 176(5):1069-76.AJ

Abstract

OBJECTIVES

Our purpose was to determine whether blockade of inducible or endothelial nitric oxide synthesis prevents maternal vasodilation and blunting of angiotensin II responsiveness in the pregnant rat.

STUDY DESIGN

Pregnant and nonpregnant rats were given (1) drinking water alone (untreated), (2) drinking water containing the inducible nitric oxide synthase inhibitor aminoguanidine (0.5 gm/L), or (3) drinking water containing the nonselective nitric oxide synthase inhibitor N omega-nitro-L-arginine methyl ester (0.5 gm/L) from postmating days 5 to 21. On days 7, 14, and 20, 24-hour urinary nitrate-nitrite excretion, urine protein concentration, hematocrit, mean arterial blood pressure, and pressor responses to angiotensin II (12.5 to 200 ng/kg) were measured. On day 21 litter size, fetal weight, and fetal mortality were determined.

RESULTS

Urinary nitrate-nitrite excretion was increased, and hematocrit and blood pressure were decreased by day 20 of pregnancy. Angiotensin II pressor responses were decreased on days 14 and 20 of pregnancy. Aminoguanidine slightly decreased nitrate-nitrite excretion in pregnant, but not nonpregnant rats, and abolished the late pregnancy increase. Aminoguanidine did not affect hematocrit, blood pressure, or angiotensin II responsiveness in either pregnant or nonpregnant rats. N omega-nitro-L-arginine methyl ester greatly reduced nitrate-nitrite excretion and induced hypertension in both nonpregnant and pregnant rats, but on day 20 blood pressure of the pregnant rats was significantly lower than that of the nonpregnant rats. N omega-nitro-L-arginine methyl ester increased angiotensin II responsiveness on days 14 and 20 only in the pregnant rats. N omega-nitro-L-arginine methyl ester, but not aminoguanidine, increased fetal mortality and decreased fetal weight.

CONCLUSIONS

Inducible nitric oxide synthesis accounts for increased nitrate-nitrite excretion during pregnancy. Endothelium-derived nitric oxide may attenuate angiotensin II responsiveness but does not cause vasodilation and the fall in blood pressure during the last week of gestation.

Authors+Show Affiliations

Department of Obstetrics and Gynecology, University of Tennessee, Memphis 38103, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

9166170

Citation

Lubarsky, S L., et al. "The Effect of Chronic Nitric Oxide Synthesis Inhibition On Blood Pressure and Angiotensin II Responsiveness in the Pregnant Rat." American Journal of Obstetrics and Gynecology, vol. 176, no. 5, 1997, pp. 1069-76.
Lubarsky SL, Ahokas RA, Friedman SA, et al. The effect of chronic nitric oxide synthesis inhibition on blood pressure and angiotensin II responsiveness in the pregnant rat. Am J Obstet Gynecol. 1997;176(5):1069-76.
Lubarsky, S. L., Ahokas, R. A., Friedman, S. A., & Sibai, B. M. (1997). The effect of chronic nitric oxide synthesis inhibition on blood pressure and angiotensin II responsiveness in the pregnant rat. American Journal of Obstetrics and Gynecology, 176(5), 1069-76.
Lubarsky SL, et al. The Effect of Chronic Nitric Oxide Synthesis Inhibition On Blood Pressure and Angiotensin II Responsiveness in the Pregnant Rat. Am J Obstet Gynecol. 1997;176(5):1069-76. PubMed PMID: 9166170.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The effect of chronic nitric oxide synthesis inhibition on blood pressure and angiotensin II responsiveness in the pregnant rat. AU - Lubarsky,S L, AU - Ahokas,R A, AU - Friedman,S A, AU - Sibai,B M, PY - 1997/5/1/pubmed PY - 1997/5/1/medline PY - 1997/5/1/entrez SP - 1069 EP - 76 JF - American journal of obstetrics and gynecology JO - Am J Obstet Gynecol VL - 176 IS - 5 N2 - OBJECTIVES: Our purpose was to determine whether blockade of inducible or endothelial nitric oxide synthesis prevents maternal vasodilation and blunting of angiotensin II responsiveness in the pregnant rat. STUDY DESIGN: Pregnant and nonpregnant rats were given (1) drinking water alone (untreated), (2) drinking water containing the inducible nitric oxide synthase inhibitor aminoguanidine (0.5 gm/L), or (3) drinking water containing the nonselective nitric oxide synthase inhibitor N omega-nitro-L-arginine methyl ester (0.5 gm/L) from postmating days 5 to 21. On days 7, 14, and 20, 24-hour urinary nitrate-nitrite excretion, urine protein concentration, hematocrit, mean arterial blood pressure, and pressor responses to angiotensin II (12.5 to 200 ng/kg) were measured. On day 21 litter size, fetal weight, and fetal mortality were determined. RESULTS: Urinary nitrate-nitrite excretion was increased, and hematocrit and blood pressure were decreased by day 20 of pregnancy. Angiotensin II pressor responses were decreased on days 14 and 20 of pregnancy. Aminoguanidine slightly decreased nitrate-nitrite excretion in pregnant, but not nonpregnant rats, and abolished the late pregnancy increase. Aminoguanidine did not affect hematocrit, blood pressure, or angiotensin II responsiveness in either pregnant or nonpregnant rats. N omega-nitro-L-arginine methyl ester greatly reduced nitrate-nitrite excretion and induced hypertension in both nonpregnant and pregnant rats, but on day 20 blood pressure of the pregnant rats was significantly lower than that of the nonpregnant rats. N omega-nitro-L-arginine methyl ester increased angiotensin II responsiveness on days 14 and 20 only in the pregnant rats. N omega-nitro-L-arginine methyl ester, but not aminoguanidine, increased fetal mortality and decreased fetal weight. CONCLUSIONS: Inducible nitric oxide synthesis accounts for increased nitrate-nitrite excretion during pregnancy. Endothelium-derived nitric oxide may attenuate angiotensin II responsiveness but does not cause vasodilation and the fall in blood pressure during the last week of gestation. SN - 0002-9378 UR - https://www.unboundmedicine.com/medline/citation/9166170/The_effect_of_chronic_nitric_oxide_synthesis_inhibition_on_blood_pressure_and_angiotensin_II_responsiveness_in_the_pregnant_rat_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0002-9378(97)70404-6 DB - PRIME DP - Unbound Medicine ER -