Adenosine and ATP produce vasoconstriction in the feline pulmonary vascular bed by different mechanisms.
It has been reported recently that adenosine and ATP produce dose- and tone-dependent responses in the feline pulmonary vascular (PV) bed. The present study was undertaken to investigate the mechanisms mediating vasoconstrictor (VC) responses to adenosine and ATP in the intact-chest, spontaneously breathing cat under conditions of controlled blood flow and constant left atrial pressure. The order of potency of adenosine receptor agonists to produce VC in the PV bed was the selective adenosine A1 receptor agonist R-phenylisopropyladenosine greater than the mixed A1, A2 receptor agonist, adenosine greater than the selective adenosine A2 receptor agonist, 2-phenylaminoadenosine. The dose-related increase in lobar arterial pressure in response to adenosine was blocked by an adenosine (P1) receptor antagonist, BWA1433U, the cyclooxygenase inhibitor, meclofenamate, and the thromboxane A2 receptor antagonist, SQ29548. The order of potency of ATP analogs to produce VC in the PV bed was alpha,beta-methylene ATP (alpha,beta-meATP) much greater than beta,tau-methylene ATP greater than ATP. BWA1433U inhibited VC responses to ATP without affecting responses to its degradation-resistant analogs beta,tau-methylene ATP and alpha,beta-meATP. In the presence of BWA1433U and a continuous intralobar infusion of the selective 5'-nucleotidase inhibitor, alpha,beta-methyleneadenosine-5'-diphosphate, ATP VC responses are significantly enhanced compared to those after BWA1433U. alpha,beta-Methyleneadenosine-5'-diphosphate had no effect on the VC response to U44069 after BWA1433U. Meclofenamate significantly inhibited the vasoconstrictor responses to ATP but not to alpha,beta-meATP.(ABSTRACT TRUNCATED AT 250 WORDS)
Neely
C F
CF
Department of Anesthesia, University of Pennsylvania School of Medicine, Philadelphia.
Haile
D M
DM
Cahill
B E
BE
Kadowitz
P J
PJ
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology*; D000244:Adenosine Diphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002415:Cats; D016861:Cyclooxygenase Inhibitors; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines / Q000494:pharmacology; D008168:Lung / Q000098:blood supply*; D008469:Meclofenamic Acid / Q000494:pharmacology; D010660:Phenylisopropyladenosine / Q000494:pharmacology; D058914:Purinergic Antagonists; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors; D011983:Receptors, Purinergic / Q000187:drug effects / Q000502:physiology; D017482:Receptors, Thromboxane; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology; D014970:Xanthines / Q000494:pharmacology
D019086:Bridged Bicyclo Compounds, Heterocyclic; D016861:Cyclooxygenase Inhibitors; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines; D058914:Purinergic Antagonists; D011982:Receptors, Prostaglandin; D011983:Receptors, Purinergic; D017482:Receptors, Thromboxane; D014665:Vasodilator Agents; D014970:Xanthines; C523965:alpha,beta-methyleneadenosine 5'-diphosphate; D010660:Phenylisopropyladenosine; D008469:Meclofenamic Acid; D013928:Thromboxane A2; D000244:Adenosine Diphosphate; C045749:SQ 29548; D000255:Adenosine Triphosphate; C053414:BW A1433U; C026708:2-phenylaminoadenosine; D000241:Adenosine; C002630:alpha,beta-methyleneadenosine 5'-triphosphate