Biomaterial Database

Pharmacological probes for A1 and A2 adenosine receptors in vivo in feline pulmonary vascular bed. 1996

C F Neely, and I Matot

Department of Anesthesia, University of Pennsylvania School of Medicine, Philadelphia 19104, USA.

Under conditions of controlled pulmonary blood flow and constant left atrial pressure, adenosine produces dose-dependent, tone-dependent responses in the pulmonary vascular (PV) bed of intact-chest, spontaneously breathing cats. The potency profile for adenosine receptor agonists to produce vasoconstriction at low baseline PV tone is 5'-(N-ethylcarboxamido)adenosine > or = CGS-21680 > or = 2-chloroadenosine (2-CADO) > or = [R]-N6-(2-phenylisopropyl)adenosine (R-PIA) > or = N6-cyclopentyladenosine > adenosine > > CV-1808. After an increase in PV tone with the use of an intralobar infusion of the thromboxane mimic U-46619, the potency profile for adenosine receptor agonists to produce vasodilation at elevated PV tone is 2-CADO > or = CV-1808 > or = CGS-21680 > R-PIA > or = adenosine. The selective A1 adenosine receptor antagonists xanthine amine congener (XAC) and 8-cyclopentyl-1,3-dipropylxanthine (DP-CPX) significantly antagonize the vasoconstrictor responses of adenosine and R-PIA at low baseline PV tone while having less effect on the vasodilator responses of adenosine, 2-CADO, and R-PIA at elevated PV tone. DPCPX antagonizes the vasoconstrictor responses of CGS-21680 at low baseline PV tone. The nonselective A1 and A2 adenosine receptor antagonist BWA-1433U significantly antagonizes vasoconstrictor responses of R-PIA and vasodilator responses of adenosine, 2-CADO, and R-PIA. These data support that adenosine produces vasoconstriction at low baseline PV tone and vasodilation at elevated PV tone in the feline PV bed by acting on A1 and A2 adenosine receptors, respectively. Compared with the adenosine receptor agonists tested in this in vivo model, R-PIA and CV-1808 are the most selective adenosine receptor agonists for A1 and A2 adenosine receptors, respectively, in the feline PV bed. R-PIA, CV-1808, DPCPX, and XAC may be used in this in vivo model to define the roles of A1 and A2 adenosine receptors in acute lung injury and pathophysiological changes in the pulmonary vasculature associated with pulmonary hypertension and edema formation in the same animal model.

UI	MeSH Term	Description	Entries
D011450	Prostaglandin Endoperoxides, Synthetic	Synthetic compounds that are analogs of the naturally occurring prostaglandin endoperoxides and that mimic their pharmacologic and physiologic activities. They are usually more stable than the naturally occurring compounds.	Prostaglandin Endoperoxide Analogs,Prostaglandin Endoperoxide Analogues,Synthetic Prostaglandin Endoperoxides,Analogues, Prostaglandin Endoperoxide,Endoperoxide Analogues, Prostaglandin,Endoperoxides, Synthetic Prostaglandin
D011652	Pulmonary Circulation	The circulation of the BLOOD through the LUNGS.	Pulmonary Blood Flow,Respiratory Circulation,Circulation, Pulmonary,Circulation, Respiratory,Blood Flow, Pulmonary,Flow, Pulmonary Blood,Pulmonary Blood Flows
D001808	Blood Vessels	Any of the tubular vessels conveying the blood (arteries, arterioles, capillaries, venules, and veins).	Blood Vessel,Vessel, Blood,Vessels, Blood
D002415	Cats	The domestic cat, Felis catus, of the carnivore family FELIDAE, comprising over 30 different breeds. The domestic cat is descended primarily from the wild cat of Africa and extreme southwestern Asia. Though probably present in towns in Palestine as long ago as 7000 years, actual domestication occurred in Egypt about 4000 years ago. (From Walker's Mammals of the World, 6th ed, p801)	Felis catus,Felis domesticus,Domestic Cats,Felis domestica,Felis sylvestris catus,Cat,Cat, Domestic,Cats, Domestic,Domestic Cat
D004305	Dose-Response Relationship, Drug	The relationship between the dose of an administered drug and the response of the organism to the drug.	Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
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
D013928	Thromboxane A2	An unstable intermediate between the prostaglandin endoperoxides and thromboxane B2. The compound has a bicyclic oxaneoxetane structure. It is a potent inducer of platelet aggregation and causes vasoconstriction. It is the principal component of rabbit aorta contracting substance (RCS).	Rabbit Aorta Contracting Substance,A2, Thromboxane
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
D014661	Vasoconstriction	The physiological narrowing of BLOOD VESSELS by contraction of the VASCULAR SMOOTH MUSCLE.	Vasoconstrictions
D014662	Vasoconstrictor Agents	Drugs used to cause constriction of the blood vessels.	Vasoactive Agonist,Vasoactive Agonists,Vasoconstrictor,Vasoconstrictor Agent,Vasoconstrictor Drug,Vasopressor Agent,Vasopressor Agents,Vasoconstrictor Drugs,Vasoconstrictors,Agent, Vasoconstrictor,Agent, Vasopressor,Agents, Vasoconstrictor,Agents, Vasopressor,Agonist, Vasoactive,Agonists, Vasoactive,Drug, Vasoconstrictor,Drugs, Vasoconstrictor