Vascular endothelin responsiveness and receptor characteristics in vitro and effects of endothelin receptor blockade in vivo in cyclosporin hypertension.
1. The aim of these studies was to determine the role of endothelin in cyclosporin A ([CsA], 10 mg/kg per day, s.c., for 30 days) hypertension in the rat. 2. There were no significant differences in plasma endothelin concentrations, in vitro mesenteric vascular membrane [125I]-endothelin-1 (ET-1) binding characteristics or myographic vascular responses to endothelin-1 between the CsA and control groups (systolic blood pressure 135 +/- 1 vs 127 +/- 1 mmHg, respectively, P < 0.001). 3. Twenty-four hours after selective endothelin type A receptor blockade in vivo with BQ123, blood pressure in CsA hypertensive rats was lowered to levels of normotensive controls. 4. These results suggest that changes in endothelin synthesis rather than changes in vascular sensitivity and/or ET-1 receptor characteristics may contribute to CsA-induced hypertension.
Phillips
P A
PA
Department of Medicine, University of Melbourne, Austin Hospital, Heidelberg, Victoria, Australia.
Rolls
K A
KA
Burrell
L M
LM
Casley
D
D
Aldred
K L
KL
Hardy
K J
KJ
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D016572:Cyclosporine / Q000097:blood / Q000633:toxicity*; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000378:metabolism / Q000502:physiology*; D005260:Female; D006973:Hypertension / Q000139:chemically induced* / Q000503:physiopathology*; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D051381:Rats; D017208:Rats, Wistar; D017466:Receptors, Endothelin / Q000502:physiology*; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology
D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D007457:Iodine Radioisotopes; D017466:Receptors, Endothelin; D016572:Cyclosporine