Studies with endothelin-3 and endothelin-1 on rat blood pressure and isolated tissues: evidence for multiple endothelin receptor subtypes.
In an anesthetized rat, endothelin-1 (ET-1) causes a rapid, transient fall in blood pressure followed by a large, sustained rise. Rat endothelin-3 (ET-3) differs from porcine endothelin-1 (ET-1) by six amino acids and is 20 times less potent at contracting rat aortic strips. The comparative effects of ET-3 and ET-1 on blood pressure were studied in anesthetized rats in which the arterial blood pressure was continually monitored. Dose-response curves for the contraction of rat stomach strips, guinea pig ileum, and guinea pig trachea were also constructed. In the anesthetized rat, ET-3 was slightly (but not significantly) less potent than ET-1 at producing the transient blood pressure fall but was three times less potent at causing the subsequent rise. The two peptides were equipotent at contracting rat stomach strips but ET-3 was 10 times less potent at contracting the guinea pig ileum. Rat ET-3 was less potent at contracting the guinea pig trachea and had a lower maximal effect. These results suggest the existence of multiple receptor subtypes for ET.
Spokes
R A
RA
Department of Medicine, Royal Postgraduate Medical School, Hammersmith Hospital, London, England.
Ghatei
M A
MA
Bloom
S R
SR
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D016232:Endothelins; D005260:Female; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D010455:Peptides / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000378:metabolism*; D013270:Stomach / Q000187:drug effects; D014132:Trachea / Q000187:drug effects / Q000378:metabolism
D016232:Endothelins; D010455:Peptides; D011956:Receptors, Cell Surface