| Popis: |
The mechanisms that mediate relaxation induced by ATP and adenosine (Ado) were studied in the rabbit femoral artery. Responses to ATP were found to be endothelium-dependent and mediated through the P2 receptor. In response to ATP, we found increases in cyclic GMP levels of cultured aortic smooth muscle cells and femoral artery rings. These increases in cyclic GMP levels were present only in the intact artery rings or in smooth muscle cells mixed or cocultured with aortic endothelium. The rise in cyclic GMP levels preceded relaxation to ATP and was abolished by either denuding the femoral of endothelium or preincubating with ETYA, ad by not having endothelial cells present in cell culture systems. ATP-induced relaxations and cyclic GMP accumulation were abolished by the P2 receptor antagonist ANAPP3 but not by theophyl-line. In contrast, relaxations to Ado were not affected by removal of the endothelium. We measured increases in cyclic AMP levels which preceded response to Ado. Both responses were attenuated by the P1 receptor antagonist, theophylline. The use of structural analogues of Ado allowed further characterization of the receptor involved as the A2 type, the stimulatory receptor for the adenylate cyclase system. Specific A2 analogues caused greater increases in cyclic AMP levels which correlated well with relaxation. In conclusion, in the rabbit femoral artery ATP is an endothelium-dependent vasodilator, causing release of endothelium-derived relaxing factor which increases smooth muscle cyclic GMP. Ado acts independently of the endothelium, to cause A2 receptor-mediated increases in smooth muscle cyclic AMP levels and relaxation. |
