ATP is involved in myocardial and vascular effects of exogenous bradykinin in ejecting guinea pig heart.
It has recently been reported that bradykinin induces selective left ventricular (LV) relaxation in isolated guinea pig hearts via the release of nitric oxide. Exogenous bradykinin also induces vasodilation, which is only partly due to nitric oxide release. In the present study we investigated the role of adenyl purines on these bradykinin-induced effects. Isolated ejecting guinea pig hearts were studied. LV pressure was monitored by a 2-Fr micromanometer-tipped catheter. ATP concentrations were measured using a luciferin-luciferase assay. Bradykinin (1 and 100 nM) caused a progressive acceleration of LV relaxation together with a transient increase in coronary flow. These effects were inhibited by the nonselective P(2) purinoceptor antagonist suramin (1 microM, n = 6) but were unaffected by the selective P(2x) purinoceptor antagonist pyridoxal phosphate 6-azophenyl-2',4'-disulfonic acid (1 microM, n = 6). These myocardial and vascular effects of bradykinin were associated with increased ATP levels in coronary effluent. These data suggest that the selective enhancement of LV relaxation and rise in coronary flow induced by exogenous bradykinin involve endogenous ATP and the subsequent stimulation of P(2) purinoceptors.
Anning
P B
PB
Cardiovascular Sciences Group, Department of Pharmacology and Therapeutics, University of Wales College of Medicine, Cardiff CF4 4XN, United Kingdom.
Prendergast
B D
BD
MacCarthy
P A
PA
Shah
A M
AM
Buss
D C
DC
Lewis
M J
MJ
D000255:Adenosine Triphosphate / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D003331:Coronary Vessels / Q000187:drug effects* / Q000378:metabolism; D006168:Guinea Pigs; D066298:In Vitro Techniques; D009200:Myocardial Contraction / Q000502:physiology*; D009206:Myocardium / Q000378:metabolism*; D058919:Purinergic P2 Receptor Antagonists; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D013498:Suramin / Q000494:pharmacology; D013599:Systole; D016277:Ventricular Function, Left / Q000187:drug effects
D058919:Purinergic P2 Receptor Antagonists; C077792:pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid; D011732:Pyridoxal Phosphate; D013498:Suramin; D000255:Adenosine Triphosphate; D001920:Bradykinin