Colitis-induced alterations in adrenergic control of circular smooth muscle in vitro in rats

The present study investigated inflammation-induced changes in adrenergic r egulation of smooth muscle. Colitis was induced in rats by intrarectal admi nistration of trinitrobenzenesulfonic acid in ethanol. After 4 h (acute) or 7 days (chronic), in vitro isometric tension was measured in strips of cir cular smooth muscle taken from the distal colon. In controls, the major inh ibitory control of smooth muscle responses to nerve stimulation was mediate d by nitric oxide and beta adrenergic receptors. There was less evidence of alpha adrenergic control. Studies with the beta (3) receptor antagonist cy anopindolol and the beta (3) receptor agonist BRL37344 revealed that beta a drenergic regulation of spontaneous contractions and responses to nerve sti mulation were mediated primarily by the beta (3) adrenoreceptor. Both acute and chronic colitis significantly increased responses to electrical field stimulation. This effect was attributed to a loss of inhibitory nitrergic r egulation as well as to selective changes in the beta adrenergic control of colonic circular smooth muscle. Inflammation did not alter alpha adrenergi c control. Chronic colitis also decreased the sensitivity to nerve stimulat ion and pharmacological contractile agents. Acute and chronic inflammation reduced the ability of BRL37344 to inhibit contractions in response to nerv e stimulation. In addition, in inflamed colon, BRL37344 was less effective in relaxing carbachol-induced precontractions. Finally, inflammation result ed in a loss of the ability of the cyanopindolol to increase the amplitude of both spontaneous contractions and contractions in response to nerve stim ulation. These effects indicated that colitis induced a down-regulation of inhibitory beta (3) adrenergic control of colonic smooth muscle function. T his loss of adrenergic regulation may contribute to the diarrhea in inflamm atory bowel disease.