title: Rat intestinal mast cell amines are released during nitric oxide synthase inhibition in vitro.
abstract: Inhibition of nitric oxide synthase increases microvascular permeability in rat small intestinal villi. To determine the mechanism(s) whereby this occurs we have perfused the vasculature of rat isolated small intestines with a gelatin-containing physiological salt solution. Inclusion of N-nitro-L-argintne methyl ester (L-NAME, 100 muM) or indomethacin (1 muM) in the perfusate increased leakage of injected colloidal carbon into microvessel walls. Pre-treatment with sodium nitroprusside (10 muM) significantly reduced the effects of both L-NAME and indomethacin, whereas carbacyclin (1 muM) only reduced the effects of indomethacin. PD151242 (1 muM) showed some antagonism towards the effects of L-NAME, but nordihydroguaiaretic acid (3 muM) was inactive. Pre-tment with cyproheptadine (10 muM) reduced the effects of both L-NAME and indomethacin, and also significantly reduced background (control) colloidal carbon leakage. Small intestines from polymixin B-treated rats showed significantly reduced colloidal carbon leakage in response to L-NAME. This suggests that the leakage-enhancing effects of both L-NAME and indomethacin in this preparation may be mediated by mast cell-derived amines.
authors.affiliation: Department of Pharmaceutical Sciences School of Applied Sciences De Montfort University Leicester LE1 9BH UK.
authors.forename: A M
authors.initials: AM
authors.lastname: Northover
authors.forename: B J
authors.initials: BJ
authors.lastname: Northover