title: Endothelin and blood pressure regulation in the female rat: studies in normal pregnancy and with nitric oxide synthase inhibition-induced hypertension.
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.affiliation: Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Northwestern University Medical School, Evanston Northwestern Healthcare, IL 60201, USA.
authors.forename: L G
authors.initials: LG
authors.lastname: Thaete
authors.forename: M G
authors.initials: MG
authors.lastname: Neerhof
mesh_terms: 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
chemical_list: D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D004791:Enzyme Inhibitors; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester