Nitrergic inhibition of migrating myoelectric complex in the rat is mediated by vasoactive intestinal peptide.
The role of vasoactive intestinal peptide (VIP) for the action of nitric oxide (NO) as a nonadrenergic noncholinergic inhibitory mediator was investigated regarding effects on migrating myoelectric complex (MMC) in rat. Animals were supplied with implanted bipolar electrodes at 5, 15 and 25 cm distal to pylorus for electromyography of small intestine. First, basal recordings with saline were followed by intravenous infusions of glyceryl trinitrate or VIP at different infusion rates to achieve dose-response relationships. Second, effects of different doses of the nitric oxide synthase inhibitor, N omega-nitro-L-arginine (L-NNA) were studied. Third, the action of L-NNA (1 mg kg-1) on the effect of VIP (500 pmol kg-1 min-1), and of the VIP receptor antagonist (4-Cl-D-Phe6, Leu17), VIP (45 nmol 20 min-1), on the action of glyceryl trinitrate (44 nmol kg-1 min-1) was investigated. Glyceryl trinitrate prolonged the MMC cycle length from 16.3 +/- 1.3 to 44.9 +/- 8.0 min (P < 0.001), while VIP completely disrupted the MMC for the whole infusion period (P < 0.05). Higher doses of either compound induced quiescence. L-NNA shortened MMC cycle length from 14.7 +/- 1.2 to 8.6 +/- 1.4 min (P < 0.05), increased its propagation velocity from 2.0 +/- 0.4 to 18.3 +/- 8.4 cm min-1 (P < 0.01) and increased calculated length from 6.3 +/- 1.0 to 55.4 +/- 18.4 cm (P < 0.01). Pretreatment with (4-Cl-D-Phe6, Leu17) VIP blocked the inhibitory action of glyceryl trinitrate and preserved MMC pattern (P < 0.05). In contrast, L-NNA had no effect on the inhibition of MMC caused by VIP. Our results indicate that inhibition of MMC is related to production of NO, which may mediate its actions through VIP.
Hellström
P M
PM
Department of Internal Medicine, Karolinska Hospital, Karolinska Institutet, Stockholm, Sweden.
Ljung
T
T
D000818:Animals; D005769:Gastrointestinal Motility / Q000187:drug effects*; D008297:Male; D016065:Myoelectric Complex, Migrating / Q000187:drug effects*; D005996:Nitroglycerin / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*
D014660:Vasoactive Intestinal Peptide; D005996:Nitroglycerin