Increased endogenous nitric oxide release by iron chelation and purinergic activation in the rat carotid body.

Abstract

We examined the hypothesis that hypoxic chemotransduction with stabilization of HIF-1 and activation of purinoceptors stimulate the endogenous NO production in the rat carotid body. The effects of blockade of purinoceptors with suramin, or blockade of HIF-1alpha hydroxylation by suppressing prolyl hydroxylase (PAH) activity on the endogenous NO release measured electrochemically by microsensor inserted into the isolated carotid body superfused with bicarbonate-buffer were examined. Suramin did not change the resting NO level under normoxic conditions but it significantly decreased the hypoxia-induced NO elevation in a dose-dependent manner. Suramin (100muM) blocked the NO response to acute hypoxia by 53%. Intracellular iron chelator, ciclopirox olamine (CPX) significantly increased the resting NO release close to the hypoxic level, which was reversed by FeSO(4) or blocked by L-NMMA. Also, PAH inhibition with dimethy-loxalylglycine (DMOG) moderately increased the resting NO release. In the presence of CPX and DMOG the resting NO release was increased to the hypoxic level. Collectively, results suggest that iron chelation and purinoceptor stimulation play a role in the hypoxic chemotransduction for an increase in the endogenous NO production in the rat carotid body.