Heterogeneity of alpha 1-adrenoceptor subtypes involved in adrenergic contractions of dog blood vessels. 1994

Y Kohno, and H Saito, and M Takita, and S Kigoshi, and I Muramatsu
Department of Otorhinolaryngology, Fukui Medical School, Japan.

1. We determined the alpha 1-adrenoceptor subtypes involved in adrenergic contractions of eight different blood vessels isolated from the dog. 2. Noradrenaline produced concentration-dependent contractions in all the blood vessels tested, which were competitively inhibited by prazosin, WB4101, HV723 and 5-methylurapidil. However, there was considerable difference between the vessels with regard to the pKB values for all the antagonists. The alpha 1-adrenoceptors of dog vertebral and carotid arteries had high affinity for prazosin (pKB > 9.0) but low affinity for WB4101 (< 8.5), 5-methylurapidil (< 7.5) and HV723 (< or = 8.5). By contrast, HV723 had higher affinity (> 9.0) than prazosin (< 8.3), WB4101 (< 8.7) and 5-methylurapidil (< 8.2) in the portal vein, mesenteric artery and vein, and renal artery. In the femoral artery and vein, however, the four antagonists showed pKB values in the range 8.0-8.7. 3. Chloroethylclonidine (10 microM) produced a remarkable reduction of the contractile responses to noradrenaline in the vertebral and carotid arteries as compared with those in the other vessels. Nifedipine inhibited the responses to noradrenaline in all the tissues tested, and had marked effects in the portal vein. 4. Sympathetic adrenergic contractions induced by transmural electrical stimulation were also inhibited by prazosin and HV723 at different potencies among tissues. The relative potencies of both the antagonists paralleled the relationship in inhibiting the responses to exogenous noradrenaline in each vessel. 5. According to recent alpha l-adrenoceptor subclassification, the present results suggest that the contractions of blood vessels induced by endogenous and exogenous noradrenaline are mediated through different alpha l-adrenoceptor subtypes heterogeneously distributed in each vessel; presumably, the alpha 1 B subtype in the carotid and vertebral arteries, the alpha IN subtype in the visceral region and the alpha IL subtype in the femoral region. Regionally different expression of alpha 1-adrenoceptor subtypes may be in part associated with the regional heterogeneity of sympathetic responses in the blood vessels.

UI MeSH Term Description Entries
D008297 Male Males
D009543 Nifedipine A potent vasodilator agent with calcium antagonistic action. It is a useful anti-anginal agent that also lowers blood pressure. Adalat,BAY-a-1040,Bay-1040,Cordipin,Cordipine,Corinfar,Fenigidin,Korinfar,Nifangin,Nifedipine Monohydrochloride,Nifedipine-GTIS,Procardia,Procardia XL,Vascard,BAY a 1040,BAYa1040,Bay 1040,Bay1040,Monohydrochloride, Nifedipine,Nifedipine GTIS
D009638 Norepinephrine Precursor of epinephrine that is secreted by the ADRENAL MEDULLA and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers, and of the diffuse projection system in the brain that arises from the LOCUS CERULEUS. It is also found in plants and is used pharmacologically as a sympathomimetic. Levarterenol,Levonorepinephrine,Noradrenaline,Arterenol,Levonor,Levophed,Levophed Bitartrate,Noradrenaline Bitartrate,Noradrénaline tartrate renaudin,Norepinephrin d-Tartrate (1:1),Norepinephrine Bitartrate,Norepinephrine Hydrochloride,Norepinephrine Hydrochloride, (+)-Isomer,Norepinephrine Hydrochloride, (+,-)-Isomer,Norepinephrine d-Tartrate (1:1),Norepinephrine l-Tartrate (1:1),Norepinephrine l-Tartrate (1:1), (+,-)-Isomer,Norepinephrine l-Tartrate (1:1), Monohydrate,Norepinephrine l-Tartrate (1:1), Monohydrate, (+)-Isomer,Norepinephrine l-Tartrate (1:2),Norepinephrine l-Tartrate, (+)-Isomer,Norepinephrine, (+)-Isomer,Norepinephrine, (+,-)-Isomer
D011224 Prazosin A selective adrenergic alpha-1 antagonist used in the treatment of HEART FAILURE; HYPERTENSION; PHEOCHROMOCYTOMA; RAYNAUD DISEASE; PROSTATIC HYPERTROPHY; and URINARY RETENTION. Furazosin,Minipress,Pratsiol,Prazosin HCL,Prazosin Hydrochloride,HCL, Prazosin,Hydrochloride, Prazosin
D004146 Dioxanes Compounds that contain the structure 1,4-dioxane.
D004285 Dogs The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065) Canis familiaris,Dog
D004558 Electric Stimulation Use of electric potential or currents to elicit biological responses. Stimulation, Electric,Electrical Stimulation,Electric Stimulations,Electrical Stimulations,Stimulation, Electrical,Stimulations, Electric,Stimulations, Electrical
D005260 Female Females
D000097 Acetonitriles Compounds in which a methyl group is attached to the cyano moiety. Cyanomethane,Cyanomethanes,Ethane Nitriles,Methyl Cyanide,Methyl Cyanides,Cyanide, Methyl,Cyanides, Methyl,Nitriles, Ethane
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

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