Superoxide dismutase mimetic tempol inhibits hypoxic pulmonary vasoconstriction in rats independently on either nitric oxide production or basal tone of pulmonary vessels

Abstract

Hypoxic pulmonary vasoconstriction (HPV) is regulated by changes in the production of and interactions among reactive oxygen species (ROS). There is a controversy as to whether HPV is mediated by an increase or a decrease in ROS production. Also, the role of nitric oxide (NO) in HPV remains unclear. We investigated whether the inhibition of HPV by the antioxidant tempol was dependent on the concentration of NO, and how its effect was influenced by increased basal pulmonary vascular tone.In isolated rat lungs we measured vasoconstrictor responses to acute hypoxia before and after administration of tempol during perfusion with or without L‐NAME and after increase of basal vascular tone in the perfused lungs by increasing the potassium ion concentration in the perfusate by 15 mmol/l.Administration of tempol significantly decreased vasoconstriction response to acute hypoxic challenge both in controls (89% less) and in L‐NAME group (100% less), the vasoconstrictor response did not differ significantly between these groups. The administration of tempol significantly decreased HPV both in K+ treated (96% less) and in K+ non‐treated group (68% less), the vasoconstrictor response did not differ significantly between these groups.Inhibition of HPV by the SOD mimetic tempol does not depend on either NO production or basal tone of the pulmonary vessels.GACR 305/05/0672, GAUK 7415/2007