Inhibitory effect of 4‐aminopyridine on responses of the basilar artery to nitric oxide

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Abstract
Voltage‐dependent K+ channels are present in cerebral arteries and may modulate vascular tone. We used 200 μM 4‐aminopyridine (4‐AP), thought to be a relatively selective inhibitor of voltage‐dependent K+ channels at this concentration, to test whether activation of these channels may influence baseline diameter of the basilar artery and dilator responses to nitric oxide (NO) and cyclic GMP in vivo. Using a cranial window in anaesthetized rats, topical application of 4‐AP to the basilar artery (baseline diameter=240±5 μm, mean±s.e.mean) produced 10±1% constriction. Sodium nitroprusside (a NO donor), acetylcholine (which stimulates endothelial release of NO), 8‐bromo cyclic GMP (a cyclic GMP analogue), cromakalim (an activator of ATP‐sensitive K+ channels) and papaverine (a non‐NO, non‐K+ channel‐related vasodilator) produced concentration‐dependent vasodilator responses that were reproducible. Responses to 10 and 100 nM nitroprusside were inhibited by 4‐AP (20±4 vs 8±2% and 51±5 vs 33±5%, respectively, n=10; PH‐[1,2,4]oxadiazolo[4,3‐a]quinoxalin‐1‐one (an inhibitor of soluble guanylate cyclase; 16±4 vs 1±1% and 44±7 vs 7±1%; n=10; P+ channels by NO/cyclic GMP. British Journal of Pharmacology (1999) 126, 1437–1443; doi:10.1038/sj.bjp.0702439