NITRIC-OXIDE MEDIATES INTESTINAL HYPEREMIC RESPONSES TO INTRALUMINAL BILE-OLEATE

It has long been recognized that intestinal blood flow increases at me altimes. Mesenteric hyperaemia is also evoked by activation of sensory peptidergic nerves. Our studies explored the possible role of endogen ous nitric oxide (NO) in the rat intestinal vasodilator response to lu minal instillation of an oleic acid plus bile mixture before and after acute intrajejunal instillation of capsaicin and after chronic pretre atment with capsaicin. In anaesthetized rats we measured jejunal blood flow (BF) with an ultrasonic Doppler flowmeter and systemic aterial p ressure (AP) with a pressure transducer. Intestinal perfusion with 80 mM oleic acid in bile increased BF by 98 +/- 12%. Instillation of 4 mg of capsaicin into the jejunal lumen initially increased BF by 42 +/- 9% but was followed by vasoconstriction. Inhibition of NO synthase wit h 25 mg/kg i.v. N-nitro-L-arginine (L-NNA) decreased BF by 27 +/- 5% a nd increased AP by 37 +/- 11%. After treatment with L-NNA and after ac ute and chronic administration of capsaicin, the bile-oleate-induced m aximal increases in BF above control levels were 42 +/- 7%, 65 +/- 12% , and 58 +/- 8%, respectively. The observed inhibitory effect of L-NNA on the intestinal hyperaemic response to the bile-oleate mixture was reversed by pretreatment with L-arginine (100 mg/kg i.v.). In capsaici n pretreated rats the subsequent bile-oleate-induced hyperaemia was re duced in magnitude but the inhibitory effects of L-NNA were proportion ately the same as in animals not receiving capsaicin. These findings s upport the hypothesis that NO is involved with bile-oleate-induced mes enteric hyperaemia.