Role of cGMP versus 20-HETE in the vasodilator response to nitric oxide inrat cerebral arteries

This study examined the response to nitric oxide (NO) in rat middle cerebra l arteries (MCA). NO donors increased the activity of a 205-pS K+ channel r ecorded from vascular smooth muscle (VSM) cells isolated from MCA 10-fold. Blockade of guanylyl cyclase activity with 1H-[1,2,4] oxadiazole[4,3-a] qui noxalin-1-one (ODQ, 10(-5) M) did not alter the effect of NO on this channe l. In contrast, adding 20-hydroxyeicosatetraenoic acid (20-HETE) to the bat h (10(-7) M) abolished the response to NO. NO donors also increased the dia meter of serotonin-preconstricted MCA to 85% of control. Blockade of K+ cha nnels with iberiotoxin or a high-K+ medium reduced this response by 50%. OD Q (10(-5) M) reduced this response by 47 +/- 3%, whereas preventing the fal l of 20-HETE levels reduced the response by 59 +/- 2% (n = 5). Blockade of both pathways eliminated the response to NO donors. These results indicate that activation of K+ channels contributes 50% to vasodilator response to N O in rat MCA. This is mediated by a fall in 20-HETE levels rather than a ri se in cGMP levels or a direct effect of NO.