Biomaterial Database

8-Bromo cyclic GMP mimics the actions of nitroglycerin in modulating responses produced by full and partial alpha-adrenoceptor agonists in canine saphenous vein. 1988

H Eskinder, and G J Gross

Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee 53226.

The purpose of the present study was to determine whether 8-bromo cyclic GMP (8-Br cGMP) mimics the actions of nitroglycerin (GTN) in inhibiting alpha-1 versus alpha-2 adrenoceptor-mediated constrictor responses in canine saphenous vein. Phenylephrine (PE) and L-dobutamine were used as full and partial alpha-1 adrenoceptor agonists, respectively, and B-HT 920 was employed as a selective alpha-2 adrenoceptor agonist. The ability of 8-Br cGMP and GTN to inhibit vasoconstrictor responses to a standard agonist concentration of PE, L-dobutamine and B-HT 920 was determined. 8-Br cGMP like GTN produced a selective antagonism of alpha-2-mediated responses of B-HT 920 and had minimal effects on alpha-1-induced constrictor responses of phenylephrine. However, when a portion of the alpha-1-adrenoceptor pool was inactivated by phenoxybenzamine (POB) (5 x 10(-8) M, 1 x 10(-7) M) 8-Br cGMP like GTN produced a significant depression of responses to PE. In addition, contractions produced by L-dobutamine, a selective partial alpha-1 adrenoceptor agonist (no alpha receptor reserve), were highly sensitive to inhibition by 8-Br cGMP and GTN. These results suggest that the presence of a large alpha-1-adrenoceptor reserve to PE concealed an underlying functional antagonism to alpha-1-adrenoceptor-mediated responses by GTN and 8-Br cGMP. The similarity in the efficacy and potency of these two agents (8-Br cGMP and GTN) suggests that the effects of GTN in canine saphenous vein may be the result of an increase in the intracellular concentration of cGMP.

UI	MeSH Term	Description	Entries
D010656	Phenylephrine	An alpha-1 adrenergic agonist used as a mydriatic, nasal decongestant, and cardiotonic agent.	(R)-3-Hydroxy-alpha-((methylamino)methyl)benzenemethanol,Metaoxedrin,Metasympatol,Mezaton,Neo-Synephrine,Neosynephrine,Phenylephrine Hydrochloride,Phenylephrine Tannate,Neo Synephrine,Tannate, Phenylephrine
D004280	Dobutamine	A catecholamine derivative with specificity for BETA-1 ADRENERGIC RECEPTORS. It is commonly used as a cardiotonic agent after CARDIAC SURGERY and during DOBUTAMINE STRESS ECHOCARDIOGRAPHY.	Dobucor,Dobuject,Dobutamin Fresenius,Dobutamin Hexal,Dobutamin Solvay,Dobutamin-ratiopharm,Dobutamina Inibsa,Dobutamina Rovi,Dobutamine (+)-Isomer,Dobutamine Hydrobromide,Dobutamine Hydrochloride,Dobutamine Lactobionate,Dobutamine Phosphate (1:1) Salt, (-)-Isomer,Dobutamine Tartrate,Dobutamine Tartrate (1:1), (R-(R,R))-Isomer,Dobutamine Tartrate (1:1), (S-(R,R))-Isomer,Dobutamine, (-)-Isomer,Dobutamine, Phosphate (1:1) Salt (+)-Isomer,Dobutrex,Lilly 81929,Oxiken,Posiject,Dobutamin ratiopharm,Hydrobromide, Dobutamine,Hydrochloride, Dobutamine,Lactobionate, Dobutamine,Tartrate, Dobutamine
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
D005996	Nitroglycerin	A volatile vasodilator which relieves ANGINA PECTORIS by stimulating GUANYLATE CYCLASE and lowering cytosolic calcium. It is also sometimes used for TOCOLYSIS and explosives.	Glyceryl Trinitrate,Anginine,Dynamite,Gilustenon,Nitrangin,Nitro-Bid,Nitro-Dur,Nitrocard,Nitroderm,Nitroderm TTS,Nitroglyn,Nitrol,Nitrolan,Nitrong,Nitrospan,Nitrostat,Perlinganit,Susadrin,Sustac,Sustak,Sustonit,Transderm Nitro,Tridil,Trinitrin,Trinitrolong,Nitro Bid,Nitro Dur,NitroBid,NitroDur,Trinitrate, Glyceryl
D006152	Cyclic GMP	Guanosine cyclic 3',5'-(hydrogen phosphate). A guanine nucleotide containing one phosphate group which is esterified to the sugar moiety in both the 3'- and 5'-positions. It is a cellular regulatory agent and has been described as a second messenger. Its levels increase in response to a variety of hormones, including acetylcholine, insulin, and oxytocin and it has been found to activate specific protein kinases. (From Merck Index, 11th ed)	Guanosine Cyclic 3',5'-Monophosphate,Guanosine Cyclic 3,5 Monophosphate,Guanosine Cyclic Monophosphate,Guanosine Cyclic-3',5'-Monophosphate,3',5'-Monophosphate, Guanosine Cyclic,Cyclic 3',5'-Monophosphate, Guanosine,Cyclic Monophosphate, Guanosine,Cyclic-3',5'-Monophosphate, Guanosine,GMP, Cyclic,Guanosine Cyclic 3',5' Monophosphate,Monophosphate, Guanosine Cyclic
D000316	Adrenergic alpha-Agonists	Drugs that selectively bind to and activate alpha adrenergic receptors.	Adrenergic alpha-Receptor Agonists,alpha-Adrenergic Receptor Agonists,Adrenergic alpha-Agonist,Adrenergic alpha-Receptor Agonist,Receptor Agonists, Adrenergic alpha,Receptor Agonists, alpha-Adrenergic,alpha-Adrenergic Agonist,alpha-Adrenergic Agonists,alpha-Adrenergic Receptor Agonist,Adrenergic alpha Agonist,Adrenergic alpha Agonists,Adrenergic alpha Receptor Agonist,Adrenergic alpha Receptor Agonists,Agonist, Adrenergic alpha-Receptor,Agonist, alpha-Adrenergic,Agonist, alpha-Adrenergic Receptor,Agonists, Adrenergic alpha-Receptor,Agonists, alpha-Adrenergic,Agonists, alpha-Adrenergic Receptor,Receptor Agonist, alpha-Adrenergic,Receptor Agonists, alpha Adrenergic,alpha Adrenergic Agonist,alpha Adrenergic Agonists,alpha Adrenergic Receptor Agonist,alpha Adrenergic Receptor Agonists,alpha-Agonist, Adrenergic,alpha-Agonists, Adrenergic,alpha-Receptor Agonist, Adrenergic,alpha-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
D012501	Saphenous Vein	The vein which drains the foot and leg.	Saphenous Veins,Vein, Saphenous,Veins, Saphenous
D014661	Vasoconstriction	The physiological narrowing of BLOOD VESSELS by contraction of the VASCULAR SMOOTH MUSCLE.	Vasoconstrictions
D014664	Vasodilation	The physiological widening of BLOOD VESSELS by relaxing the underlying VASCULAR SMOOTH MUSCLE.	Vasodilatation,Vasorelaxation,Vascular Endothelium-Dependent Relaxation,Endothelium-Dependent Relaxation, Vascular,Relaxation, Vascular Endothelium-Dependent,Vascular Endothelium Dependent Relaxation