The effect of an endothelin antagonist on blood pressure in a rat model of preeclampsia.
OBJECTIVE
We attempted to determine the role of endothelin in a previously characterized animal model of preeclampsia by studying the effect of a specific endothelin antagonist, BQ123, on blood pressure.


METHODS
A preeclampsia-like condition was induced by infusing pregnant rats with the nitric oxide synthase inhibitor N(G)-nitro-L -arginine methyl ester. Osmotic minipumps were inserted subcutaneously into timed pregnant Harlan-Sprague-Dawley rats on day 17 of pregnancy (term, 22 days). The pumps were loaded to continuously deliver either vehicle (control group) or N(G)-nitro-L -arginine methyl ester 50 mg/d, either alone or with BQ123 at 0.5 mg/d. In a similar but separate experiment, the dose of BQ123 was increased to 1 mg/d. Blood pressure was measured with the tail-cuff method before pump insertion and then daily until postpartum day 2.


RESULTS
Except for a decrease on the day after pump insertion, BQ123 0.5 mg/d had no significant effect on the hypertension induced by N(G)-nitro-L -arginine methyl ester. At the higher dose, however, BQ123 significantly attenuated the increase in blood pressure induced by N(G)-nitro-L -arginine methyl ester during most of the study period.


CONCLUSIONS
The effect of nitric oxide inhibition can be successfully attenuated by the use of an endothelin antagonist, thereby supporting the role of endothelin in the hypertension described with the preeclampsialike condition seen in pregnant rats.
Olson
G L
GL
Division of Materna;-Fetal Medicine, Department of Obstetrics and Gynecology, The University of Texas Medical Branch, Galveston, USA.
Saade
G R
GR
Buhimschi
I
I
Chwalisz
K
K
Garfield
R E
RE
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D004195:Disease Models, Animal; D016232:Endothelins / Q000037:antagonists & inhibitors* / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005865:Gestational Age; D006973:Hypertension / Q000139:chemically induced; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010456:Peptides, Cyclic / Q000008:administration & dosage / Q000494:pharmacology; D011225:Pre-Eclampsia / Q000139:chemically induced / Q000503:physiopathology*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley
D016232:Endothelins; D004791:Enzyme Inhibitors; D010456:Peptides, Cyclic; D019001:Nitric Oxide Synthase; C072247:cyclo(Trp-Asp-Pro-Val-Leu); D019331:NG-Nitroarginine Methyl Ester