Effects of preload and eicosanoid synthesis inhibition on rat aortic smooth muscle sensitivity

Concentration-response curves to serotonin and phenylephrine were obtained from aortic strips subjected to low (0.75 g) and high (3.0) preloads in the presence and absence of eicosanoid synthesis inhibitors. The sensitivity of the strips to both agonists was greater in the high preload strips. The cyclooxygenase inhibitor, indomethacin (28 microM), shifted the serotonin concentration-response curves to the right. However, the preload effect still remained. The lipoxygenase inhibitor, nordihydroguaiaretic acid (10 microM), not only decreased sensitivity to serotonin and phenylephrine, but eliminated the preload effect as well. These results suggest that 1) both cyclooxygenase and lipoxygenase metabolites affect the sensitivity of isolated arterial smooth muscle to vasoactive agents, and 2) lipoxygenase, but not cyclooxygenase, metabolites may play a role in the effect of preload on arterial smooth muscle sensitivity.