Endothelium-derived relaxing factor participates in the increased blood flow in response to pentagastrin in the rat stomach mucosa.
The stimulation of gastric-acid secretion by pentagastrin, a synthetic analogue of the endogenous peptide gastrin, is associated with an increased blood flow to the stomach mucosa, commonly referred to as functional hyperaemia. There are at least two potent vasodilator substances, the local release of which from endothelial cells could contribute to this hyperaemia, endothelium-derived relaxing factor (EDRF) and prostacyclin. EDRF has been identified as nitric oxide, released enzymatically from the guanidino group of L-arginine. In the present studies, the involvement of prostacyclin in the pentagastrin-induced increase in stomach blood flow was eliminated by using the cyclo-oxygenase inhibitor indomethacin. Thus this work was designed to elucidate the participation of EDRF/NO in the pentagastrin-induced hyperaemia and not its relative importance to prostacyclin. The increase in blood flow to the gastric mucosa in response to pentagastrin was measured by laser Doppler flowmetry in situ. Inhibition of EDRF/NO biosynthesis with the L-arginine analogues NG-monomethyl-L-arginine (MeArg) or N omega-nitro-L-arginine (NO2Arg) significantly attenuated (by more than 80%) the increase in mucosal blood flow in response to pentagastrin. However, infusions of the natural substrate L-arginine reversed the inhibitor effect of MeArg on pentagastrin-induced increase in mucosal blood flow. Local intra-arterial injections of the endothelium-independent vasodilator glyceryl trinitrate produced a dose-related increase in blood flow to the rat stomach mucosa that was unaffected by infusion of MeArg. Thus, in the absence of prostacyclin, EDRF/NO participates in the pentagastrin-induced increase in blood flow to the rat stomach mucosa.
Walder
C E
CE
William Harvey Research Institute, St Bartholomew's Hospital Medical College, Charterhouse Square, London, U.K.
Thiemermann
C
C
Vane
J R
JR
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure / Q000502:physiology*; D007213:Indomethacin / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000098:blood supply*; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D010418:Pentagastrin / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D012039:Regional Blood Flow / Q000187:drug effects; D019323:omega-N-Methylarginine
D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D010418:Pentagastrin; D007213:Indomethacin