Vascular responsiveness of constant flow perfused arteries with intact endothelium.

We have devised a perfused artery preparation, in which one can conveniently assess vasoactivity to agents (a) in the presence and absence of a functionally intact endothelium within the same vessel, and (b) when added to the luminal or abluminal (i.e., adventitial) surface of the vessel. Moreover, utilizing stainless steel cannulas of various calibers, one can routinely perfuse vessels ranging from less than 1 mm to over 4 mm in internal diameter. By moderating the pulsatile nature of the constant flow perfusion, one can retain a functionally intact endothelium (i.e., at totally damped perfusion) or one can abolish endothelial modulation of vasoactive agents (i.e., a pulsatile perfusion). The integrity of the endothelium was confirmed by histological methods. Using perfused cat carotid arteries preconstricted with U-46619, a stable prostaglandin-endoperoxide analog which maintains a stable vasoconstriction, acetylcholine dilated carotid arteries perfused at non-pulsatile flows, but not at pulsatile flows, indicating the endothelium dependent nature of the vasodilation produced by ACh. This was confirmed with the calcium ionophore A-23187, a non-receptor endothelium dependent vasodilator. However, calcium channel blockers (e.g., nimodipine) prostacyclin analogs (e.g., iloprost) or vasodilator nitrates (e.g., sodium nitrite at pH 2.0) produced equivalent dilations in the presence and absence of a functional intact endothelium. This preparation allows for convenient use of single dose application of pharmacologic agents as well as cumulative dose-response relationships.