| Abstrakt: |
We describe a simple, functional approach to defining the relative contribution of endothelium-dependent hyperpolarization (presumably mediated by a factor, EDHF) and endothelium-derived nitric oxide (EDNO) to acetylcholine (ACh) and histamine relaxations of isolated perfused rat mesenteric resistance arterial bed. In physiologic salt solution (PSS), ACh- and his-tamine-induced vasodilations of cirazoline-preconstricted mesenteric arterial bed were only partially attenuated by 50 μMNw-nitro-L-arginine methyl ester (L-NAME). The L-NAME-resistant component was abolished by 0.5 μMapamin but not by 250 nMdendrotoxin or 10 μMglyburide, thus indicating a role for apamin-sensitive K+channels in mediating the effects of the putative EDHF. Changing membrane potential by varying [K+] decreased L-NAME-resistant vasodilation, and showed a modest L-NAME-induced increase in the basal perfusion pressure that was not observable in normal PSS. Vasodilator responses during cirazoline-induced tonus in 20 mMK+and normal PSS were superimposable, but responses to ACh and histamine in 20 mMK+were profoundly more sensitive to L-NAME than were those in normal PSS media. ACh responses during 20-mMK +PSS perfusion and presumably mediated by EDNO and those resistant to L-NAME and putatively mediated by EDHF were antagonized by graded concentrations of p-fluoro-hexahydro-siladifenidol (p-F-HHSiD), but not pirenzepine. Therefore, we concluded that (a) perfused rat mesenteric arterial bed releases both EDHF and EDNO in response to ACh and histamine, (b) EDHF plays a dominant role in maintenance of the basal perfusion pressure in this vascular bed, and (c) both EDHF and EDNO relaxations are mediated by activation of M3muscarinic cholinoceptors. |
