Altered mechanisms underlying hypoxic dilation of skeletal muscle resistance arteries of hypertensive versus normotensive Dahl rats

Objective: To determine mechanisms underlying hypoxic dilation of skeletal muscle resistance arteries from normotensive (NT) and hypertensive (HT) Dah l salt-sensitive (SS) rats. Methods: Isolateral graeilis arteries (GA) from both rat groups were viewed via television microscopy and vascular responses to a reduction in PO2 fro m 145 mm Hg to 40 mm Hg were measured with a video micrometer. Responses we re determined following endothelium removal and following inhibition of spe cific biochemical pathways regulating vascular tone. Results: Hypoxic dilation was impaired in HT rats versus NT controls. Endot helium removal abolished hypoxic dilation in NT rats, although a significan t dilation to hypoxia remained in vessels from HT animals. Inhibition of cy tochrome P450 (CP450) 4A enzymes blunted hypoxic dilation in both groups, w hile inhibition of epoxyeicosatrienoic acid (EET) production impaired respo nses in NT rats only. Inhibition of 20-hydroxyeicosatetraenoic acid (20-HET E) production or blockade of membrane receptors for 20-HETE reduced hypoxic dilation in HT rats, with minimal effects in NT animals. Nitric oxide synt hase inhibition had no effect on hypoxic dilation in either group, while cy cloxygenase inhibition significantly reduced this response in both groups. Conclusions: These results suggest that the mechanisms of hypoxic dilation in GA from NT Dahl-SS rats are altered with HT, impairing the response to r educed PO2. While hypoxia induced substantial prostanoid release in both gr oups, the role of CP450 4A enzymes is shifted from EET production in NT rat s toward inhibition of 20-HETE, production in HT rats.