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Endothelin and blood pressure regulation in the female rat: studies in normal pregnancy and with nitric oxide synthase inhibition-induced hypertension.
Hypertens Pregnancy. 2000; 19(2):233-47.HP

Abstract

OBJECTIVE

To evaluate the role of endothelin (ET) in blood pressure regulation in normal pregnant and nonpregnant rats and with nitric oxide synthase (NOS) inhibition.

METHODS

Pregnant and nonpregnant Sprague-Dawley rats were treated for 7 days with an ET(A)-selective (A-127722 or FR-139317), ET(B)-selective (A-192621), or ET(A)/ET(B) nonselective (A-182086) endothelin receptor antagonist, and/or with the NOS inhibitor, N(omega)-nitro-L-arginine methyl ester (L-NAME, 2. 5 mg/kg/h). In pregnant rats, the ET antagonists and L-NAME were administered from gestational day 14 through day 21 (term = 22 days). All rats received indwelling arterial catheters for blood pressure measurement. Mean arterial pressures were recorded on infusion days 1, 4, and 7 and these data were compared by analysis of variance among experimental groups with p < 0.05 considered significant.

RESULTS

The ET(A) receptor antagonism lowered blood pressure in both pregnant and nonpregnant rats (p < 0.05), whereas ET(B) antagonism resulted in hypertension (p < 0.001). ET(B) antagonism-induced hypertension was attenuated by pregnancy (p < 0. 001). Hypertension was induced in all rats treated with L-NAME (p < 0.001). Endothelin receptor antagonism, regardless of specificity, did not ameliorate L-NAME-induced hypertension in pregnant or nonpregnant female rats. The only observed effect of ET(A) antagonism on NOS inhibition-induced hypertension was the prevention of a continued rise at infusion day 7 in nonpregnant rats.

CONCLUSIONS

Endothelin, acting via both the ET(A) and ET(B) receptors, contributes to blood pressure homeostasis in pregnant and nonpregnant rats. Endothelin receptor antagonism does not ameliorate NOS-inhibition-induced hypertension in pregnant rats.

Authors+Show Affiliations

Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Northwestern University Medical School, Evanston Northwestern Healthcare, IL 60201, USA.No affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

10877991

Citation

Thaete, L G., and M G. Neerhof. "Endothelin and Blood Pressure Regulation in the Female Rat: Studies in Normal Pregnancy and With Nitric Oxide Synthase Inhibition-induced Hypertension." Hypertension in Pregnancy, vol. 19, no. 2, 2000, pp. 233-47.
Thaete LG, Neerhof MG. Endothelin and blood pressure regulation in the female rat: studies in normal pregnancy and with nitric oxide synthase inhibition-induced hypertension. Hypertens Pregnancy. 2000;19(2):233-47.
Thaete, L. G., & Neerhof, M. G. (2000). Endothelin and blood pressure regulation in the female rat: studies in normal pregnancy and with nitric oxide synthase inhibition-induced hypertension. Hypertension in Pregnancy, 19(2), 233-47.
Thaete LG, Neerhof MG. Endothelin and Blood Pressure Regulation in the Female Rat: Studies in Normal Pregnancy and With Nitric Oxide Synthase Inhibition-induced Hypertension. Hypertens Pregnancy. 2000;19(2):233-47. PubMed PMID: 10877991.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Endothelin and blood pressure regulation in the female rat: studies in normal pregnancy and with nitric oxide synthase inhibition-induced hypertension. AU - Thaete,L G, AU - Neerhof,M G, PY - 2000/7/6/pubmed PY - 2000/8/19/medline PY - 2000/7/6/entrez SP - 233 EP - 47 JF - Hypertension in pregnancy JO - Hypertens Pregnancy VL - 19 IS - 2 N2 - OBJECTIVE: To evaluate the role of endothelin (ET) in blood pressure regulation in normal pregnant and nonpregnant rats and with nitric oxide synthase (NOS) inhibition. METHODS: Pregnant and nonpregnant Sprague-Dawley rats were treated for 7 days with an ET(A)-selective (A-127722 or FR-139317), ET(B)-selective (A-192621), or ET(A)/ET(B) nonselective (A-182086) endothelin receptor antagonist, and/or with the NOS inhibitor, N(omega)-nitro-L-arginine methyl ester (L-NAME, 2. 5 mg/kg/h). In pregnant rats, the ET antagonists and L-NAME were administered from gestational day 14 through day 21 (term = 22 days). All rats received indwelling arterial catheters for blood pressure measurement. Mean arterial pressures were recorded on infusion days 1, 4, and 7 and these data were compared by analysis of variance among experimental groups with p < 0.05 considered significant. RESULTS: The ET(A) receptor antagonism lowered blood pressure in both pregnant and nonpregnant rats (p < 0.05), whereas ET(B) antagonism resulted in hypertension (p < 0.001). ET(B) antagonism-induced hypertension was attenuated by pregnancy (p < 0. 001). Hypertension was induced in all rats treated with L-NAME (p < 0.001). Endothelin receptor antagonism, regardless of specificity, did not ameliorate L-NAME-induced hypertension in pregnant or nonpregnant female rats. The only observed effect of ET(A) antagonism on NOS inhibition-induced hypertension was the prevention of a continued rise at infusion day 7 in nonpregnant rats. CONCLUSIONS: Endothelin, acting via both the ET(A) and ET(B) receptors, contributes to blood pressure homeostasis in pregnant and nonpregnant rats. Endothelin receptor antagonism does not ameliorate NOS-inhibition-induced hypertension in pregnant rats. SN - 1064-1955 UR - https://www.unboundmedicine.com/medline/citation/10877991/Endothelin_and_blood_pressure_regulation_in_the_female_rat:_studies_in_normal_pregnancy_and_with_nitric_oxide_synthase_inhibition_induced_hypertension_ L2 - https://www.tandfonline.com/doi/full/10.1081/prg-100100139 DB - PRIME DP - Unbound Medicine ER -