Requirement for endothelium-derived nitric oxide in vasodilation 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 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 microM), NG-nitro-L-arginine (L-NOARG, 100 microM), 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 dilation 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.(ABSTRACT TRUNCATED AT 250 WORDS)