Nitric oxide mediates C5a-induced vasodilation in the small intestine.
OBJECTIVE
This study was designed to investigate the microvascular responses of the small intestine to complement C5a and to define the role of nitric oxide in the C5a-induced response.


METHODS
Male Sprague-Dawley rats were anesthetized with pentobarbital, and a loop of small intestine was exteriorized and suffused with Krebs solution. The diameters of large and small arterioles of the small intestinal wall were measured with in vivo videomicroscopy following the application of experimental mediators. Four 1-hr C5a dose-response trials were performed (10(-14) M, 10(-12) M, 10(-10) M, and 10(-8) M). Then, we completed acetylcholine dose-response curves with and without N omega-nitro-L-arginine (N-Arg) to document the adequacy of nitric oxide synthase inhibition. The microvascular response to the topical application of C5a (10(-12) M) was recorded in the presence of 2 x 10(-4) M N-Arg. Additionally, experiments of C5a-induced response with N-Arg were repeated in the presence of L-arginine (L-Arg; the precursor of nitric oxide synthesis) or with systemic administration of superoxide dismutase (SOD).


RESULTS
(1) C5a induces a dose-dependent vasodilation in the small intestine, and the maximal vasodilation occurs in A3 arterioles at C5a concentration of 10(-12) M; (2) N-Arg inhibits the Ach-induced vasodilation in the rat small intestine; and (3) L-Arg or SOD partially reverses the inhibitory effect of N-Arg.


CONCLUSIONS
Nitric oxide mediates the C5a-induced vasodilation in small intestinal microvessels. Superoxide is, at least partially, responsible for the vasoconstrictor response to C5a in the presence of N-Arg.
Department of Physiology and Biophysics, University of Louisville, Kentucky, USA.
H Y
HY
Luo
W B
WB
Wead
S
S
Yang
M A
MA
Wilson
P D
PD
Harris
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D015936:Complement C5a / Q000037:antagonists & inhibitors / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007421:Intestine, Small / Q000098:blood supply*; D008297:Male; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology; D018715:Microscopy, Video; D009569:Nitric Oxide / Q000502:physiology*; D019335:Nitroarginine; D051381:Rats; D017207:Rats, Sprague-Dawley; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
D004791:Enzyme Inhibitors; D019335:Nitroarginine; D009569:Nitric Oxide; D015936:Complement C5a; D001120:Arginine