Impairment of flow-induced dilation of skeletal muscle arterioles with elevated oxygen in normotensive and hypertensive rats.
The effects of elevated PO(2) on flow-induced dilation of in situ skeletal muscle arterioles was assessed in cremaster muscle preparations from spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. Blood flow increases in selected arterioles were initiated by occlusion of a parallel daughter branch from a parent arteriole. Changes in the diameter of the perfused arteriole were measured with a video micrometer and erythrocyte velocity was measured using optical Doppler velocimetry. Superfusate PO(2) was controlled by changing the O(2) concentration (0% O(2) or 21% O(2)) of the equilibration gas mixture. The increase in arteriolar diameter during occlusion was reduced in SHR compared to WKY rats, resulting in an elevated wall shear rate in SHR. Elevated PO(2) decreased flow-induced dilation in both groups and increased wall shear rate during parallel occlusion. An inhibitor of the formation of 20-HETE via cytochrome P450-4A enzymes (P450), dibromododecenyl methylsulfimide, minimized O(2)-induced constriction of arterioles and prevented the O(2)-induced decrease in flow-induced dilation and the increase in wall shear rate in both SHR and WKY rats. These results suggest that: (1) flow-induced dilation of in situ skeletal muscle arterioles is impaired in SHR compared to WKY, (2) elevated O(2) compromises flow-induced dilation in both groups, (3) 20-HETE contributes to both the O(2)-induced increases in resting tone and the reduced flow-induced dilation of cremasteric arterioles with elevated PO(2).
Frisbee
J C
JC
Department of Physiology, Milwaukee, Wisconsin 53226, USA.
Roman
R J
RJ
Falck
J R
JR
Linderman
J R
JR
Lombard
J H
JH
D000577:Amides / Q000494:pharmacology; D000818:Animals; D001160:Arterioles / Q000502:physiology; D042926:Cytochrome P-450 CYP4A; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018056:Hemorheology; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism; D006973:Hypertension / Q000235:genetics / Q000503:physiopathology*; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D018715:Microscopy, Video; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors / Q000378:metabolism; D018482:Muscle, Skeletal / Q000098:blood supply*; D010100:Oxygen / Q000097:blood / Q000494:pharmacology*; D010313:Partial Pressure; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013450:Sulfones / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*
D000577:Amides; D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D006893:Hydroxyeicosatetraenoic Acids; D013450:Sulfones; C055987:20-hydroxy-5,8,11,14-eicosatetraenoic acid; D003577:Cytochrome P-450 Enzyme System; C117975:DDMS; D006899:Mixed Function Oxygenases; D042926:Cytochrome P-450 CYP4A; D010100:Oxygen