In vitro simultaneous measurements of relaxation and nitric oxide concentration in rat superior mesenteric artery

J Physiol. 1999 Apr 1;516 ( Pt 1)(Pt 1):271-82. doi: 10.1111/j.1469-7793.1999.271aa.x.

Abstract

1. The relationship between nitric oxide (NO) concentration measured with an NO-specific microelectrode and endothelium-dependent relaxation was investigated in isolated rat superior mesenteric artery contracted with 1 microM noradrenaline. 2. Acetylcholine (10 microM) induced endothelium-dependent simultaneous increases in luminal NO concentration of 21 +/- 6 nM, and relaxations with pD2 values and maximum of 6.95 +/- 0.32 and 97.5 +/- 0.7 % (n = 7), respectively. An inhibitor of NO synthase, N G-nitro-L-arginine (L-NOARG, 100 microM) inhibited the relaxations and increases in NO concentration induced by acetylcholine. 3. Oxyhaemoglobin (10 microM) reversed the relaxations and increases in NO concentrations induced by acetylcholine, S-nitroso-N-acetylpenicillamine (SNAP) and S-morpholino-sydnonimine (SIN-1), but not the relaxations induced with forskolin. Oxyhaemoglobin also decreased the NO concentration below baseline level. 4. In the presence of L-NOARG (100 microM), a small relaxation to acetylcholine (10 microM) of noradrenaline-contracted segments was still seen; oxyhaemogobin inhibited this relaxation and decreased the NO concentration by 14 +/- 4 nM (n = 4). 5. The NO concentration-relaxation relationship for acetylcholine resembled that for SNAP and SIN-1 more than for authentic NO. Thus while 7-17 nM NO induced half-maximal relaxations in response to SNAP or SIN-1, 378 +/- 129 nM NO (n = 4) was needed for half-maximal relaxation to authentic NO. 6. The present study provides direct evidence that the relaxation of the rat superior mesenteric artery with the endothelium-dependent vasodilator acetylcholine is correlated to the endogeneous release of NO. The study also suggests that NO mediates the L-NOARG-resistant relaxations in this artery, and that there is a basal NO release.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / pharmacology
  • Animals
  • Endothelium, Vascular / enzymology
  • Endothelium, Vascular / physiology
  • Enzyme Inhibitors / pharmacology
  • In Vitro Techniques
  • Male
  • Mesenteric Artery, Superior / chemistry
  • Mesenteric Artery, Superior / metabolism
  • Mesenteric Artery, Superior / physiology*
  • Microelectrodes
  • Molsidomine / analogs & derivatives
  • Molsidomine / pharmacology
  • Muscle Relaxation / physiology
  • Muscle, Smooth, Vascular / chemistry
  • Muscle, Smooth, Vascular / metabolism
  • Muscle, Smooth, Vascular / physiology*
  • Nitric Oxide / analysis
  • Nitric Oxide / metabolism*
  • Nitric Oxide Donors / pharmacology
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Nitric Oxide Synthase Type III
  • Nitroarginine / pharmacology
  • Oxyhemoglobins / pharmacology
  • Penicillamine / analogs & derivatives
  • Penicillamine / pharmacology
  • Rats
  • Rats, Wistar
  • S-Nitroso-N-Acetylpenicillamine

Substances

  • Enzyme Inhibitors
  • Nitric Oxide Donors
  • Oxyhemoglobins
  • Nitroarginine
  • Nitric Oxide
  • linsidomine
  • S-Nitroso-N-Acetylpenicillamine
  • Molsidomine
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type III
  • Nos3 protein, rat
  • Penicillamine
  • Acetylcholine