Endothelial Cell Pathway for Conduction of Hyperpolarization and Vasodilation Along Hamster Feed Artery

Abstract

Abstract-Acetylcholine (ACh) evokes the conduction of vasodilation along resistance microvessels. However, it is not known which cell layer (endothelium or smooth muscle) serves as the conduction pathway. In isolated, cannulated feed arteries (Ϸ70 m in diameter at 75 mm Hg; length Ϸ4 mm) of the hamster retractor muscle, we tested the hypothesis that endothelial cells provide the pathway for conduction. Microiontophoresis of ACh (500 ms, 500 nA) onto the distal end of a feed artery evoked hyperpolarization (Ϫ13Ϯ2 mV) of both cell layers with vasodilation (15Ϯ1 m) along the entire vessel. To selectively damage endothelial cells (confirmed by loss of vasodilation to ACh and labeling of disrupted cells with propidium iodide), an air bubble was perfused through a portion of the vessel lumen, or a 70-kDa fluorescein-conjugated dextran (FCD) was illuminated within a segment (300 m) of the lumen. After endothelial cell damage, hyperpolarization and vasodilation conducted up to, but not through, the treated segment. To selectively damage smooth muscle cells (confirmed by loss of vasoconstriction to phenylephrine and labeling with propidium iodide), FCD was perifused around the vessel and illuminated. Vasodilation and hyperpolarization conducted past the disrupted smooth muscle cells without attenuation. We conclude that endothelial cells provide the pathway for conducting hyperpolarization and vasodilation along feed arteries in response to ACh. (Circ Res. 2000;86:94-100.)

Coordination of Vasomotor Responses by the Endothelium

“…28,51,65,66 This research suggests that the mechanism leading to hyperpolarization is not crucial in determining spread, only in initiating cell-cell coupling. However, some agonists may stimulate additional signaling pathways that can either augment (eg, by cAMP) 67 or reduce (eg, by α1-adrenoceptor stimulation; PKC) 68,69 the ability of hyperpolarization to spread between cells.…”

The Vascular Conducted Response in Cerebral Blood Flow Regulation

“…8,9 Conduction velocity has been estimated to 41 to 3 mm/s in intracellular Ca 2 þ or diameter measurements with limited time-resolution [10][11][12][13] and 420 to B45 mm/s in electrophysiological recordings with higher time-resolution. 14,15 For comparison, the velocity of intercellular Ca 2 þ waves spreading along arterioles has been estimated toB0.1 mm/s. 16,17 Thus, conducted vasomotor responses spread with velocities that are 1 to 3 orders of magnitude faster than the spread of intercellular Ca 2 þ waves.…”

Hypertension attenuates cell-to-cell communication in hamster retractor muscle feed arteries

“…This practical approach entailed stimulating a small proportion of a resistance artery with agents known to change smooth muscle or endothelial cell membrane potential. These electrical events are thought to spread along resistance arteries through gap junctions (8,9,31,41,42), although other mechanisms of cell-to-cell communication have not been entirely excluded. As these electrical responses conduct, they elicit vasomotor responses at sites distal to the point of agent application.…”