Pharmacological Observations on the Hypotensive Action of Extracts of Teleost Fish Urophyses (Urotensin I) in the Rat

Abstract

1 Intravenous injections of urotensin I regularly caused a long-lasting, dose-related, lowering of blood pressure and an increase in heart rate in conscious rats, or a reduction in perfusion pressure in the isolated hind limb of the rat. 2 After subcutaneous administration, the hypotensive effect of urotensin I was greater in extent and in duration (> 24 hours). 3 Anaesthesia with ether, chloralose, pentobarbitone and thiobarbitone caused a decrease in blood pressure and only slightly diminished the hypotensive effect of urotensin. 4 Mecamylamine, hexamethonium, atropine, phenoxybenzamine, propranolol and diphenhydramine did not alter the effect of urotensin in conscious rats or in the isolated hind limb, although the effects of the respective agonists, i.e. nicotineL acetylcholine, noradrenaline, isoprenaline and histamine were inhibited. 5 In conscious rats, pressor effects of adrenaline, noradrenaline, nicotine and angiotensin II, and depressor effects of acetylcholine and bradykinin, were decreased or inhibited, whereas the hypotensive effect of phenoxybenzamine was potentiated by previous administration of urotensin I. Carotid occlusion reflex was partially inhibited by lower doses of urotensin and abolished by higher doses in rats lightly anaesthetized with chloralose. Urotensin elicited postural hypotension in rats anaesthetized with pentobarbitone. 6 The increase in heart rate produced by urotensin was not affected by phenoxybenzamine, but was abolished by propranolol or ganglion blocking agents (mecamylamine or hexamethonium). 7 It is concluded that urotensin elicits hypotension in the rat by a direct dilatory action on the resistance vessels causing a simultaneous reflex tachycardia.

Effects of Urotensin I on the Isolated Rat Tail Artery

“…Small contractions elicited by 10-6 Af hista- Tire evidence obtained on the isolated rat tail artery in the present experiments suggests strongly that UI elicits relaxation in isolated blood vessels, as it does vasodilation in vivo (13), by a direct action on vascular smooth muscle.…”

“…Competitive and non-competitive components o f antagonism were observed to noradrenaline-, 5-hydroxytryptamine-, and arginine vasopressin-induced contractions. Atropine caused a direct relaxation o f the isolated vascular tissues, as well as a significant potentiation o f UI responses.Urotensin 1 (U I), one o f two peptides iso lated from the urophysis o f the white sucker (Catastomus commersoni) (19) has been shown to have a long lasting hypotensive action in a number o f mammalian species (13, 15).Mecamylamine, hexamethonium bromide, propranolol and diphenhydramine did not alter the blood pressure lowering effect o f UI in conscious rats or tire perfusion pressure lowering effect in the isolated rat hind limb (13,14) suggesting that UI elicited hypotension in the rat by a direct dilatory action in the resistance vessels, accompanied by a reflex tachycardia. Close-arterial or systemic intra…”

“…Urotensin 1 (U I), one o f two peptides iso lated from the urophysis o f the white sucker (Catastomus commersoni) (19) has been shown to have a long lasting hypotensive action in a number o f mammalian species (13,15).…”

Immunohistochemical Localization of Urotensin I/Corticotropin-Releasing Factor Immunoreactivity in Neurosecretory Neurons in the Caudal Spinal Cord of Fish

“…1983 Accepted after revision: April 25, 1984 tern of interest not only from a comparative viewpoint but also as a model for the study of neurosecretion in general. In addition, its accessibility and location in a neuropil not complicated by fibers of passage make it an ideal system for the application of electrophysiological and tract tracing techniques and experimental manipulations such as deafferentation.One of the peptides isolated from the caudal neurosecre tory system, urotensin I (UI), has been shown in mammals [50] and in birds [48] to produce a pronounced lowering of blood pressure by vasodilatation [27,34] that may be some what selective for mesenteric arteries [28,35], Little has been determined about the specific role of UI in the phy siology of fish. UI acts as a mild diuretic and weak vaso pressor in freshwater-adapted Anguilla rostrata [5] and in creases plasma sodium, chloride and magnesium in saltwa ter-adapted Gillichlhyes mirabilis [4].…”

Eferências do núcleo lateral superior da oliva no rato (rattus norvegicus).

“…Os três peptídeos (CRF, Svg e Uro-I) estimulam a secreção de ACTH in vitro e in vivo no rato RIVIER et al, 1983;LEDERIS et al, 1985b) e ainda neste modelo animal a Uro-I, administrada via endovenosa, induziu um efeito hipotensivo maior e mais duradouro que o CRF (LEDERIS & MEDAKOVIC, 1974). Em cães, os mesmos efeitos hipotensivos intensos foram determinados pela Uro-I e Svg, sendo também maiores do que aqueles apresentados pelo CRF, e decorrentes de um mecanismo de dilatação da artéria mesentérica (MaCCANNELL & LEDERIS, 1977;MaCCANNELL et al, 1982;LEDERIS et al, 1985b).…”