Vasomotion consists of regular variations in the tone of blood vessels. In this study we aimed to characterize the vasomotion induced by the thromboxane A₂ mimetic U46619 in bovine conventional pulmonary arteries.

Bovine lungs were obtained fresh from the local abattoir. Ring segments of conventional arteries (0.3-0.5cm in diameter, dissected from the 3^rd and 4^th arterial generation) were mounted in organ baths. In some artery rings the intima was removed by abrading the luminal surface with forceps. The vessels were then suspended between stainless steel hooks in Krebs-Henseleit buffer (37 oC) under a tension of 2 g and gassed with a mixture of O₂:CO₂ 95%/5% v/v. The tissues were allowed to equilibrate for 1 hour before the addition of drugs. Results are means ± s.e. mean.

Low concentrations (3-8 nM) of U46619 induced a slowly developing increase in tone (maximum initial tension, 0.32±0.01gm, n=7). After 5-8 min vasomotion began, which consisted of a rapid increase in tone (3.94±0.15gm, n =7) followed by relaxation (frequency 1.61±0.03 cycles/min). The vasomotion continued for 2-3 hrs. The initial tone and the vasomotion were abolished by the TP receptor antagonist ICI 192,605 (100nM) and caffeine (10 mM). Verapamil (10 µM), the IP₃ receptor antagonist 2APB (Maruyama et al., 1997, 50 µM) and the gap junction inhibitor heptanol (Christ et al., 1999, 200 µM) abolished the vasomotion but not the initial rise in the tone.

In intima-denuded vessels or in intima-intact vessels in the presence of the K⁺ channel blockers TEA (non-selective, 3-5mM), charybdotoxin (BK_Ca and K_V, 100nM) or iberiotoxin (BK_Ca, 100nM) but not glibenclamide (K_ATP, 10 µM) or apamin (SK_Ca, 100nM), the relaxation phase of the vasomotion was lost resulting in a sustained contraction. The initial increase in tone and the vasomotion was unaffected by L-NAME (100 µM) or indomethacin (10 µM).

The present study shows that low concentrations of the U46619 induce a small increase in tone and a delayed vasomotion. The initial tone was abolished by depletion of intracellular calcium. The vasomotion require influx of calcium through the L-type channels, gap junctions and the release of intracellular calcium via IP₃ receptors. The relaxation phase of the vasomotion appears to involve hyperpolarisation mediated by BK_Ca since this phase is sensitive to charybdotoxin and iberiotoxin. The relaxation phase also requires the presence of an intact intima suggesting that intimal cells are involved in mediating this phase. In these arteries a network of interstitial cells are present in close association with the endothelium (Tracey et al., 2003). Since intimal abrasion is likely to damage both the endothelial cells and the interstitial cells it is unclear which cell type may mediate the relaxation.

Christ, G.J. et al., (1999). Am. J. Physiol. 276 H1911-H1917
Maruyama, T. et al., (1997). J. Biochem. 122(3) 498-50
Tracey, A. et al., (2003). pA 2 1(3) 034P