Heterologous desensitization of beta-adrenoceptor signal transduction in vivo. 1997

M D Travis, and E J Whalen, and S J Lewis
The Department of Pharmacology and Cardiovascular Center, The University of Iowa, Iowa City 52242, USA.

The hemodynamic actions of pituitary adenylate cyclase-activating polypeptide (PACAP-27) rapidly diminish upon repeated i.v. injection in rats treated with the nitric oxide synthase inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME). We now report that the beta-adrenoceptor agonist isoproterenol (0.5 microg/kg, i.v.) produces pronounced hypotensive and vasodilator effects in anesthetized rats pretreated with L-NAME (100 micromol/kg, i.v.). However, the hypotensive and vasodilator actions of isoproterenol were markedly diminished in L-NAME-treated rats in which tachyphylaxis to PACAP was induced immediately prior to the injection of the beta-adrenoceptor agonist. This suggests that a reduction in tissue concentrations of nitric oxide-containing factors allows tachyphylaxis to PACAP-27-mediated vasodilation to occur in vivo and that this process leads to the heterologous desensitization of beta-adrenoceptor-mediated responses.

UI MeSH Term Description Entries
D007275 Injections, Intravenous Injections made into a vein for therapeutic or experimental purposes. Intravenous Injections,Injection, Intravenous,Intravenous Injection
D007545 Isoproterenol Isopropyl analog of EPINEPHRINE; beta-sympathomimetic that acts on the heart, bronchi, skeletal muscle, alimentary tract, etc. It is used mainly as bronchodilator and heart stimulant. Isoprenaline,Isopropylarterenol,4-(1-Hydroxy-2-((1-methylethyl)amino)ethyl)-1,2-benzenediol,Euspiran,Isadrin,Isadrine,Isopropyl Noradrenaline,Isopropylnoradrenaline,Isopropylnorepinephrine,Isoproterenol Hydrochloride,Isoproterenol Sulfate,Isuprel,Izadrin,Norisodrine,Novodrin,Hydrochloride, Isoproterenol,Noradrenaline, Isopropyl,Sulfate, Isoproterenol
D009479 Neuropeptides Peptides released by NEURONS as intercellular messengers. Many neuropeptides are also hormones released by non-neuronal cells. Neuropeptide
D011943 Receptors, Adrenergic, beta One of two major pharmacologically defined classes of adrenergic receptors. The beta adrenergic receptors play an important role in regulating CARDIAC MUSCLE contraction, SMOOTH MUSCLE relaxation, and GLYCOGENOLYSIS. Adrenergic beta-Receptor,Adrenergic beta-Receptors,Receptors, beta-Adrenergic,beta Adrenergic Receptor,beta-Adrenergic Receptor,beta-Adrenergic Receptors,Receptor, Adrenergic, beta,Adrenergic Receptor, beta,Adrenergic beta Receptor,Adrenergic beta Receptors,Receptor, beta Adrenergic,Receptor, beta-Adrenergic,Receptors, beta Adrenergic,beta Adrenergic Receptors,beta-Receptor, Adrenergic,beta-Receptors, Adrenergic
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
D004791 Enzyme Inhibitors Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme
D000318 Adrenergic beta-Agonists Drugs that selectively bind to and activate beta-adrenergic receptors. Adrenergic beta-Receptor Agonists,beta-Adrenergic Agonists,beta-Adrenergic Receptor Agonists,Adrenergic beta-Agonist,Adrenergic beta-Receptor Agonist,Betamimetics,Receptor Agonists, beta-Adrenergic,Receptors Agonists, Adrenergic beta,beta-Adrenergic Agonist,beta-Adrenergic Receptor Agonist,Adrenergic beta Agonist,Adrenergic beta Agonists,Adrenergic beta Receptor Agonist,Adrenergic beta Receptor Agonists,Agonist, Adrenergic beta-Receptor,Agonist, beta-Adrenergic,Agonist, beta-Adrenergic Receptor,Agonists, Adrenergic beta-Receptor,Agonists, beta-Adrenergic,Agonists, beta-Adrenergic Receptor,Receptor Agonist, beta-Adrenergic,Receptor Agonists, beta Adrenergic,beta Adrenergic Agonist,beta Adrenergic Agonists,beta Adrenergic Receptor Agonist,beta Adrenergic Receptor Agonists,beta-Agonist, Adrenergic,beta-Agonists, Adrenergic,beta-Receptor Agonist, Adrenergic,beta-Receptor Agonists, Adrenergic
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
D013618 Tachyphylaxis Rapidly decreasing response to a drug or physiologically active agent after administration of a few doses. In immunology, it is the rapid immunization against the effect of toxic doses of an extract or serum by previous injection of small doses. (Dorland, 28th ed)
D014655 Vascular Resistance The force that opposes the flow of BLOOD through a vascular bed. It is equal to the difference in BLOOD PRESSURE across the vascular bed divided by the CARDIAC OUTPUT. Peripheral Resistance,Total Peripheral Resistance,Pulmonary Vascular Resistance,Systemic Vascular Resistance,Peripheral Resistance, Total,Resistance, Peripheral,Resistance, Pulmonary Vascular,Resistance, Systemic Vascular,Resistance, Total Peripheral,Resistance, Vascular,Vascular Resistance, Pulmonary,Vascular Resistance, Systemic

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