Potent cardiovascular effects of homologous urotensin II (UII)-related peptide and UII in unanesthetized eels after peripheral and central injections.
We cloned cDNAs encoding urotensin II (UII)-related peptide (URP) and UII in Japanese eel, Anguilla japonica, the former being the first such cloning in teleost fishes. Unlike the exclusive expression of UII in the urophysis, the URP gene was expressed most abundantly in the brain (medulla oblongata) followed by the urophysis. Peripheral injections of URP into eels increased blood pressure by 16.1 ± 0.8 mmHg at 0.1 nmol/kg in ventral aortic blood pressure (P(VA)) and with similar potency and efficacy to that of UII (relative potency of URP to UII = 0.83). URP/UII and ANG II preferentially acted on the branchial and systemic circulations, respectively, and the duration of effect was distinct among the three peptides in the order of UII (60 min) >URP (30 min) >ANG II (14 min) in P(VA). Urantide, a mammalian UII receptor antagonist, inhibited the URP effect (-63.6 ± 5.2%) to a greater extent than for UII (-39.9 ± 5.0%). URP and UII constricted isolated eel branchial and systemic arteries, showing their direct actions on the vascular smooth muscle. Central injection of URP increased blood pressure by 12.3 ± 0.8 mmHg at 50 pmol/eel in P(VA) and with similar efficacy but less potency (relative potency = 0.47) and shorter duration compared with UII. The central actions of URP/UII were more potent on the branchial circulation than on the systemic circulation, again opposite the effects of ANG II. The similar responses to peripheral and central injections suggest that peripheral hormones may act on the brain. Taken together, in eels, URP and UII are potent cardiovascular hormones like ANG II, acting directly on the peripheral vasculature, as well as a central vasomotor site, and their actions are mediated to different degrees by the UII receptor.
Laboratory of Physiology, Atmosphere and Ocean Research Institute, The University of Tokyo, 5-1-5, Kashiwanoha, Kashiwa, Chiba 277-8564, Japan. nobata@aori.u-tokyo.ac.jp
Shigenori
S
Nobata
John A
JA
Donald
Richard J
RJ
Balment
Yoshio
Y
Takei
D000595:Amino Acid Sequence; D000804:Angiotensin II / Q000008:administration & dosage / Q000494:pharmacology; D000811:Anguilla / Q000502:physiology*; D000825:Animal Structures / Q000378:metabolism; D000818:Animals; D001158:Arteries / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002320:Cardiovascular Physiological Phenomena / Q000187:drug effects*; D002490:Central Nervous System / Q000187:drug effects / Q000378:metabolism; D003001:Cloning, Molecular; D018076:DNA, Complementary; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000235:genetics; D006339:Heart Rate / Q000187:drug effects; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000494:pharmacology; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors; D014579:Urotensins / Q000008:administration & dosage / Q000235:genetics / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000008:administration & dosage / Q000494:pharmacology
D018076:DNA, Complementary; D010446:Peptide Fragments; D043562:Receptors, G-Protein-Coupled; D014579:Urotensins; D014662:Vasoconstrictor Agents; C492079:urotensin II (4-11), Pen(5)-Trp(7)-Orn(8)-; D000804:Angiotensin II; C029677:urotensin II