Journal article
Inhibitory effect of 4-aminopyridine on responses of the basilar artery to nitric oxide
British journal of pharmacology, Vol.126(6), pp.1437-1443
03/1999
DOI: 10.1038/sj.bjp.0702439
PMCID: PMC1565911
PMID: 10217538
Abstract
Voltage-dependent K
+
channels are present in cerebral arteries and may modulate vascular tone. We used 200 μ
M
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 n
M
nitroprusside were inhibited by 4-AP (20±4 vs 8±2% and 51±5 vs 33±5%, respectively,
n
=10;
P
<0.05). Responses to acetylcholine and 8-bromo cyclic GMP were also partially inhibited by 4-AP. In contrast, 4-AP had no effect on vasodilator responses to cromakalim or papaverine. These findings suggest that NO/cyclic GMP-induced dilator responses of the basilar artery are selectively inhibited by 4-aminopyridine.
Responses to nitroprusside were also markedly inhibited by 10 μ
M
1
H
-[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
<0.05).
Thus, dilator responses of the rat basilar artery to NO appear to be mediated by activation of soluble guanylate cyclase and partially by activation of a 4-aminopyridine-sensitive mechanism. The most likely mechanism would appear to be activation of voltage-dependent K
+
channels by NO/cyclic GMP.
Details
- Title: Subtitle
- Inhibitory effect of 4-aminopyridine on responses of the basilar artery to nitric oxide
- Creators
- Christopher G Sobey - Department of Pharmacology, The University of Melbourne, Parkville, Victoria 3052, AustraliaFrank M Faraci - Departments of Internal Medicine and Pharmacology, Cardiovascular Center, University of Iowa College of Medicine, Iowa City, Iowa 52242, U.S.A
- Resource Type
- Journal article
- Publication Details
- British journal of pharmacology, Vol.126(6), pp.1437-1443
- DOI
- 10.1038/sj.bjp.0702439
- PMID
- 10217538
- PMCID
- PMC1565911
- ISSN
- 0007-1188
- eISSN
- 1476-5381
- Language
- English
- Date published
- 03/1999
- Academic Unit
- Cardiovascular Medicine; Neuroscience and Pharmacology; Internal Medicine
- Record Identifier
- 9984040598002771
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