Purinergic relaxation and hyperpolarization in guinea pig and rabbit coronary artery: role of the endothelium.

Purinergic relaxation and hyperpolarization was investigated in the isolated guinea pig coronary artery (GPCA) and compared to purinergic relaxation in the rabbit coronary artery (RCA). Vessels were contracted with the histamine H1 receptor agonist 2-(2-aminoethyl)pyridine (AEP) and the actions of adenosine, AMP, ATP, 2-chloroadenosine (CIAD),2-methylthioATP (MeATP) and beta,gamma-methylene ATP compared. The order of potency with P1 agonists in GPCA was CIAD greater than adenosine = AMP and for P2y agonists it was MeATP greater than ATP greater than beta,gamma-methylene ATP. Both ATP and CIAD produced less relaxation of GPCA segments contracted with K+ (36-100 mM) than with AEP. The IC50 for CIAD, but not ATP, was increased in the GPCA with 8(p-sulfophenyl)theophylline (100 microM). Relaxations with ATP and CIAD were not different in endothelium-denuded GPCA. Methylene blue (50 microM) increased AEP contractile amplitude by 33% and increased the IC50 values for both CIAD and ATP. A similar shift in potency to purines was seen by varying AEP concentration. ATP, CIAD and MeATP also relaxed RCA. These responses were not different in endothelium-denuded vessels. Pressure application of ATP, MeATP, adenylylimidodiphosphate and to a lesser extent beta,gamma methATP transiently hyperpolarized cells in the GPCA, whereas CIAD did not. ATP hyperpolarization was enhanced in the presence of AEP and abolished after endothelium removal. The results indicate that purinergic relaxation in the GPCA and RCA is mediated by both P1 and P2y receptors located on the smooth muscle cells. In the GPCA, P1 receptors appear limited to the muscle, whereas P2y receptors are present on both muscle and endothelium.(ABSTRACT TRUNCATED AT 250 WORDS)