In many small arteries, and in arterioles, hyperpolarization spreads bi-directionally along the longitudinal axis of the vessel. Spread appears to be endothelium dependent, and is suggested to underlie spreading vasodilatation (Emerson & Segal, 2000). In rat mesenteric arteries, myoendothelial gap junctions appear to contribute to the local spread of endothelium-dependent hyperpolarization (Edwards et al. 1999). However, homocellular gap junctions are also present in this artery (Sandow & Hill, 2000), raising the possibility for spreading hyperpolarization and vasodilatation.

Male Wistar rats (200-250 g) were killed humanely. Small mesenteric arteries were isolated, and then either pinned out for intracellular recording with sharp microelectrodes or cannulated and pressurized for diameter measurements. In both cases, tissue was superfused with Mops solution containing 100 µM L-NAME at 37 °C. Either ACh or levcromakalim were applied by pressure ejection from a micropipette. Values are means ± S.E.M. ACh evoked robust hyperpolarization at the local site of application, increasing the resting potential (-48.8 ± 4.7 mV, n = 21) by 14.3 ± 1.2 mV (n = 8). The hyperpolarization spread upstream and was detected 1 mm from the point of application (6.6 ± 0.8 mV, n = 8). The conducted (but not the local) hyperpolarization was blocked by cutting the vessel between the sites of stimulation and upstream recording. The spreading hyperpolarization was correlated with dilatation, where diameter increased to 74 ± 9 % of maximum at the local site and 69 ± 5 % 1 mm upstream of the point of ACh stimulation. However, in arteries where the endothelial cells had been selectively loaded with the Ca²⁺ indicator fluo-4, no change in [Ca²⁺]_i could be detected at the upstream site, contrasting with a 22 ± 3 % increase at the local site (n = 3). Direct smooth muscle stimulation with levcromakalim also evoked both local and upstream hyperpolarization (13.0 ± 1.6 mV, n = 12 and 4.3 ± 1.0 mV, n = 9, respectively) and dilatation (90 ± 4 %, n = 4, and 70 ± 12, n = 4 % maximum, respectively). However, in arteries where the endothelium had been destroyed, while local hyperpolarization was unaltered, the upstream responses were abolished.

These data show that spreading hyperpolarization and dilatation can occur in the mesenteric artery. Further, they indicate that the route for spread is through the endothelium and that the distant dilatation does not require any spreading change in endothelial cell [Ca²⁺]_i.

This work was supported by The Wellcome Trust.