Mechanism of the pressor action of LY171555, a specific dopamine D2 receptor agonist, in the conscious rat. 1986

S Nagahama, and Y F Chen, and M D Lindheimer, and S Oparil

Administration of LY171555, a specific dopamine D2 receptor agonist, (10-1000 micrograms/kg i.v.) produced dose-related increases in mean arterial pressure in conscious Sprague-Dawley rats. Pretreatment with metoclopramide (5 mg/kg i.v.) abolished the pressor action of LY171555, whereas pretreatment with domperidone (2.5 mg/kg i.v.) and propranolol (10 mg/kg i.p.) did not affect the pressor action of LY171555. The vasopressor antagonist of arginine vasopressin (AVP), d(CH2)5Tyr(Me)AVP (10 micrograms/kg i.v.) and phenoxybenzamine (1 mg/kg i.v.) partly blocked and hexamethonium (25 mg/kg i.v.) enhanced the pressor action of LY171555. After combined treatment with both d(CH2)5Tyr(Me)AVP and phenoxybenzamine, LY171555 induced a depressor response which was completely blocked by pretreatment with domperidone. LY171555 administration induced a rapid, short-acting depressor response followed by a pressor response in conscious adrenomedullectomized Sprague-Dawley rats which was smaller in magnitude than that seen in intact Sprague-Dawley rats. LY171555 administration increased plasma norepinephrine, epinephrine and AVP in conscious Sprague-Dawley rats. These results suggest that the pressor action of LY171555 in conscious rats is dependent on activation of sympathetic outflow and AVP release through the central D2 dopaminergic system and that the central pressor effects of LY171555 could mask a depressor effect of LY171555 at the peripheral D2 dopamine receptor.

UI MeSH Term Description Entries
D008297 Male Males
D008729 Methoxamine An alpha-1 adrenergic agonist that causes prolonged peripheral VASOCONSTRICTION. Methoxamedrin,Methoxamine Hydrochloride,Metoxamine Wellcome,Vasoxin,Vasoxine,Vasoxyl,Vasylox,Hydrochloride, Methoxamine,Wellcome, Metoxamine
D008787 Metoclopramide A dopamine D2 antagonist that is used as an antiemetic. 4-Amino-5-chloro-N-(2-(diethylamino)ethyl)-2-methoxybenzamide,Cerucal,Maxolon,Metaclopramide,Metoclopramide Dihydrochloride,Metoclopramide Hydrochloride,Metoclopramide Monohydrochloride,Metoclopramide Monohydrochloride, Monohydrate,Primperan,Reglan,Rimetin,Dihydrochloride, Metoclopramide,Hydrochloride, Metoclopramide,Monohydrochloride, Metoclopramide
D010643 Phenoxybenzamine An alpha-adrenergic antagonist with long duration of action. It has been used to treat hypertension and as a peripheral vasodilator. Dibenylene,Dibenyline,Dibenziran,Dibenzylin,Dibenzyline,Dibenzyran,Phenoxybenzamine Hydrochloride,Hydrochloride, Phenoxybenzamine
D011919 Rats, Inbred Strains Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding. August Rats,Inbred Rat Strains,Inbred Strain of Rat,Inbred Strain of Rats,Inbred Strains of Rats,Rat, Inbred Strain,August Rat,Inbred Rat Strain,Inbred Strain Rat,Inbred Strain Rats,Inbred Strains Rat,Inbred Strains Rats,Rat Inbred Strain,Rat Inbred Strains,Rat Strain, Inbred,Rat Strains, Inbred,Rat, August,Rat, Inbred Strains,Rats Inbred Strain,Rats Inbred Strains,Rats, August,Rats, Inbred Strain,Strain Rat, Inbred,Strain Rats, Inbred,Strain, Inbred Rat,Strains, Inbred Rat
D011954 Receptors, Dopamine Cell-surface proteins that bind dopamine with high affinity and trigger intracellular changes influencing the behavior of cells. Dopamine Receptors,Dopamine Receptor,Receptor, Dopamine
D001794 Blood Pressure PRESSURE of the BLOOD on the ARTERIES and other BLOOD VESSELS. Systolic Pressure,Diastolic Pressure,Pulse Pressure,Pressure, Blood,Pressure, Diastolic,Pressure, Pulse,Pressure, Systolic,Pressures, Systolic
D004873 Ergolines A series of structurally-related alkaloids that contain the ergoline backbone structure. Ergoline
D006584 Hexamethonium Compounds Compounds containing the hexamethylenebis(trimethylammonium) cation. Members of this group frequently act as antihypertensive agents and selective ganglionic blocking agents. Compounds, Hexamethonium
D000313 Adrenal Medulla The inner portion of the adrenal gland. Derived from ECTODERM, adrenal medulla consists mainly of CHROMAFFIN CELLS that produces and stores a number of NEUROTRANSMITTERS, mainly adrenaline (EPINEPHRINE) and NOREPINEPHRINE. The activity of the adrenal medulla is regulated by the SYMPATHETIC NERVOUS SYSTEM. Adrenal Medullas,Medulla, Adrenal,Medullas, Adrenal

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