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) Dahl salt-sensitive (SS) rats.


METHODS
Isolated gracilis arteries (GA) from both rat groups were viewed via television microscopy and vascular responses to a reduction in PO2 from 145 mm Hg to 40 mm Hg were measured with a video micrometer. Responses were determined following endothelium removal and following inhibition of specific biochemical pathways regulating vascular tone.


RESULTS
Hypoxic dilation was impaired in HT rats versus NT controls. Endothelium removal abolished hypoxic dilation in NT rats, although a significant dilation to hypoxia remained in vessels from HT animals. Inhibition of cytochrome P450 (CP450) 4A enzymes blunted hypoxic dilation in both groups, while inhibition of epoxyeicosatrienoic acid (EET) production impaired responses in NT rats only. Inhibition of 20-hydroxyeicosatetraenoic acid (20-HETE) production or blockade of membrane receptors for 20-HETE reduced hypoxic dilation in HT rats, with minimal effects in NT animals. Nitric oxide synthase inhibition had no effect on hypoxic dilation in either group, while cyclooxygenase 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 reduced PO2. While hypoxia induces substantial prostanoid release in both groups, the role of CP450 4A enzymes is shifted from EET production in NT rats toward inhibition of 20-HETE production in HT rats.
Frisbee
J C
JC
Department of Physiology, Medical College of Wisconsin, Milwaukee 53226, USA. jfrisbee@mcw.edu
Roman
R J
RJ
Murali Krishna
U
U
Falck
J R
JR
Lombard
J H
JH
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D001158:Arteries / Q000503:physiopathology; D003577:Cytochrome P-450 Enzyme System / Q000502:physiology; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D006893:Hydroxyeicosatetraenoic Acids / Q000502:physiology; D006973:Hypertension / Q000503:physiopathology*; D000860:Hypoxia / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D051381:Rats; D020303:Rats, Inbred Dahl; D014655:Vascular Resistance; D014664:Vasodilation
D005231:Fatty Acids, Unsaturated; D006893:Hydroxyeicosatetraenoic Acids; D016718:Arachidonic Acid; C047008:17-octadecynoic acid; C055987:20-hydroxy-5,8,11,14-eicosatetraenoic acid; D003577:Cytochrome P-450 Enzyme System; D019331:NG-Nitroarginine Methyl Ester