Electromechanical and pharmacomechanical signalling pathways for conducted vasodilatation along endothelium of hamster feed arteries

Conducted vasodilatation (CVD) reflects the initiation and rapid (> mm s(-1)) spread of hyperpolarization along the endothelium and into smooth muscle. The ion channels that initiate CVD remain unclear as do signalling pathways that may complement electromechanical relaxation. Using isolated pressurized (75 mmHg; 37 degrees C) feed arteries (n = 63; diameter: rest: 53 +/- 2 mu m, maximal: 98 +/- 2 mu m) from hamster retractor skeletal muscle, we investigated the contribution of calcium-activated potassium channels (K-Ca) and endothelium-derived autacoids to CVD. Local delivery (1 mu m micropipette tip; 500-2000 ms pulse) of acetylcholine (ACh) at the downstream end initiated a local increase in endothelial cell [Ca2+](i) (Fura-PE3; Delta ratio 340/380 nm = 0.215 +/- 0.032) that preceded CVD along the entire vessel. During local perifusion with K-Ca antagonists, iberiotoxin (5 mu M) had no effect, but charybdotoxin (CTX, 5 mu M + apamin (APA, 10 mu M) abolished CVD reversibly. Remarkably, this local inhibition of K-Ca unmasked a 'slow-conducted vasodilatation' (SCVD) that spread > 1200 mu m at similar to 21 mu m s(-1) (n = 27). Recorded 500 mu m upstream from the ACh stimulus, a rise in endothelial cell [Ca2+](i) (Delta ratio 340/380 nm) = 0.146 +/- 0.017; P < 0.05) preceded SCVD (Delta diameter = 14 +/- 3 mu m) by similar to 10 s. Before K-Ca inhibition, antagonism of nitric oxide synthase (N-omega-nitro-L-arginine, 250 mu M; L-NNA) and cyclooxygenase (indomethacin, 5 mu M; INDO) had no effect on the amplitude of CVD yet response duration decreased by one-third (P < 0.05). During local CTX + APA perifusion, L-NNA + INDO abolished SCVD while conducted [Ca2+](i) responses remained intact. Thus, ACh triggers electromechanical relaxation of smooth muscle cells along the vessel initiated by local K-Ca, and the ensuing 'wave' of Ca2+ along the endothelium releases autacoids to promote pharmacomechanical relaxation.