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

• 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
• DOI: 10.1111/j.1476-5381.1994.tb13121.x
• EISSN: 1476-5381
• ISSN: 0007-1188

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.