Impairment of flow-induced dilation of skeletal muscle arterioles with elevated oxygen in normotensive and hypertensive rats

The effects of elevated PO2 on flow-induced dilation of in situ skeletal mu scle arterioles was assessed in cremaster muscle preparations from spontane ously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. Blo od flow increases in selected arterioles were initiated by occlusion of a p arallel daughter branch from a parent arteriole. Changes in the diameter of the perfused arteriole were measured with a video micrometer and erythrocy te velocity was measured using optical Doppler velocimetry. Superfusate PO2 was controlled by changing the O-2 concentration (0% O-2 or 21% O-2) of th e equilibration gas mixture. The increase in arteriolar diameter during occ lusion was reduced in SHR compared to WKY rats, resulting in an elevated wa ll shear rate in SHR. Elevated PO2 decreased flow-induced dilation in both groups and increased wall shear rate during parallel occlusion. An inhibito r of the formation of 20-HETE via cytochrome P450-4A enzymes (P450), dibrom ododecenyl methylsulfimide, minimized O-2-induced constriction of arteriole s and prevented the O-2-induced decrease in flow-induced dilation and the i ncrease 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 im paired in SI-IR compared to WKY, (2) elevated O-2 compromises flow-induced dilation in both groups, (3) 20-HETE contributes to both the O-2-induced in creases in resting tone and the reduced flow-induced dilation of cremasteri c arterioles with elevated PO2. (C) 2000 Academic Press.