Requirement for endothelium‐derived nitric oxide in vasodilatation produced by stimulation of cholinergic nerves in rat hindquarters

1 We aimed to determine whether nitric oxide (NO) and/or the endothelium is involved in cholinergic neurogenic vasodilatation in the rat isolated hindquarters. 2 The abdominal aorta was cannulated for perfusion of the rat hindquarters with Krebs bicarbonate solution containing phenylephrine, to indu...

Full description

Saved in:

Bibliographic Details
Published in:	British journal of pharmacology Vol. 112; no. 2; pp. 630 - 634
Main Authors:	Loke, K.E., Sobey, C.G., Dusting, G.J., Woodman, O.L.
Format:	Journal Article
Language:	English
Published:	Oxford, UK Blackwell Publishing Ltd 01-06-1994 Nature Publishing
Subjects:	3‐3 cholamidopropyl dimethylammonio 1‐propanesulphonate (CHAPS) Acetylcholine Biological and medical sciences Blood vessels and receptors cholinergic neurogenic dilatation endothelium Fundamental and applied biological sciences. Psychology NG‐nitro‐l‐arginine nitric oxide Vertebrates: cardiovascular system Rat Rodentia Smooth muscle Vasodilation Endothelium Muscular relaxation Vertebrata Mammalia Blood vessel Nitrogen monoxide Acetylcholine Circulatory system Cholinergic transmission
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	1 We aimed to determine whether nitric oxide (NO) and/or the endothelium is involved in cholinergic neurogenic vasodilatation in the rat isolated hindquarters. 2 The abdominal aorta was cannulated for perfusion of the rat hindquarters with Krebs bicarbonate solution containing phenylephrine, to induce basal constrictor tone. In the presence of noradrenergic neurone blockade with guanethidine (200 mg kg−1, i.p.) electrical stimulation of peri‐aortic nerves induced frequency‐dependent decreases in hindquarters perfusion pressure, indicating vasodilatation. Both the endothelium‐dependent vasodilator, acetylcholine (ACh) and the endothelium‐independent vasodilator, sodium nitroprusside (SNP) induced dose‐dependent decreases in perfusion pressure. In each experiment, responses to either nerve stimulation, ACh or SNP were recorded before and after treatment with saline vehicle, atropine (1 μm), NG‐nitro‐l‐arginine (l‐NOARG, 100 μm), l‐arginine (1 mm), l‐arginine plus l‐NOARG, or 3–3 cholamidopropyl dimethylammonio 1‐propanesulphonate (CHAPS, 30 mg). Hindquarters dilatation after each treatment was expressed as a percentage of the control response. 3 Following treatment with saline, responses to nerve stimulation and ACh were 99 ± 9% and 107 ± 10% of control, respectively demonstrating the reproducibility of these responses. Nerve stimulation‐induced dilatation was abolished by atropine (0 ± 0% of control, P < 0.05) or reduced to 14 ± 10% of control by NO synthase inhibition with l‐NOARG (P < 0.05). Dilator responses to ACh were also abolished by atropine (0 ± 0% of control, P < 0.05) or inhibited by l‐NOARG (59 ± 10% of control, P < 0.05), indicating that the neurogenic dilatation is cholinergic and is mediated by NO. The administration of the NO precursor, l‐arginine, prevented the inhibitory effect of l‐NOARG on dilator responses to nerve stimulation and ACh (l‐arginine plus l‐NOARG: 89 ± 13% and 122 ± 24% of control, respectively). In addition CHAPS, which removes endothelial cells, inhibited responses to both nerve stimulation (0 ± 0% of control, P < 0.05) and ACh (33 ± 8% of control, P<0.05). In contrast, no treatment significantly reduced the vasodilator responses to SNP. 4 These observations suggest that cholinergic neurogenic vasodilatation in the rat isolated hindquarters requires the synthesis and release of NO from the endothelium.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23
ISSN:	0007-1188 1476-5381
DOI:	10.1111/j.1476-5381.1994.tb13121.x