Endothelin and blood pressure regulation in the female rat: studies in normal pregnancy and with nitric oxide synthase inhibition-induced hypertension.
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.
Thaete
L G
LG
Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Northwestern University Medical School, Evanston Northwestern Healthcare, IL 60201, USA.
Neerhof
M G
MG
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D004791:Enzyme Inhibitors; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester