INHIBITION OF NONADRENERGIC NONCHOLINERGIC RELAXATIONS BY NITRIC-OXIDE DONORS

被引:18
作者
DEMAN, JG
BOECKXSTAENS, GE
DEWINTER, BY
MOREELS, TG
HERMAN, AG
PELCKMANS, PA
机构
[1] UNIV ANTWERP,FAC MED,DIV GASTROENTEROL,B-2610 ANTWERP,BELGIUM
[2] UNIV ANTWERP,FAC MED,DIV PHARMACOL,B-2610 ANTWERP,BELGIUM
关键词
FEEDBACK INHIBITION; NITRERGIC NERVE; NITRIC OXIDE (NO); NANC (NONADRENERGIC NONCHOLINERGIC); GASTRIC FUNDUS; (RAT);
D O I
10.1016/0014-2999(95)00420-P
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The effects of pretreatment with the nitric oxide (NO)-releasing substances 3-morpholino-sydnoninime (SIN-1) and nitroglycerin were investigated on relaxations induced by non-adrenergic non-cholinergic (NANC) nerve stimulation, authentic NO and vasoactive intestinal polypeptide (VIP) in the rat gastric fundus. Short periods of electrical stimulation (0.5-16 Hz, 1 ms, pulse trains of 10 s) induced frequency-dependent transient relaxations, previously shown to be mainly mediated by NO. Both SIN-1 (10-100 mu M) and nitroglycerin (0.5 mM) pretreatment significantly reduced these electrically induced responses to a similar extent as the inhibitor of the NO biosynthesis L-nitroarginine (30-300 mu M). Prolonged periods of electrical stimulation (16 Hz, 1 ms, pulse trains of 180 s) induced a sustained relaxation, previously shown to be mediated by NO and VIP. L-Nitroarginine (30-300 mu M) or pretreatment with SIN-1 (100 mu M) or nitroglycerin (0.5 mM) did not affect the amplitude of this relaxation but slowed down its onset. Authentic NO (0.01-10 mu M) and VIP (0.01-10 nM) induced respectively transient and sustained concentration-dependent relaxations. SIN-1 or nitroglycerin pretreatment had no effect on the concentration-response curves to NO and VIP. These results indicate that prolonged exposure to NO donors inhibits electrically induced nerve-mediated NANC relaxations without affecting the postjunctional response to NO and VIP. As similar results are obtained with NO biosynthesis inhibitors, our results illustrate a prejunctional inhibitory effect of NO on the NANC nerves of the rat gastric fundus and suggest the presence of an autoregulatory mechanism for the nitrergic innervation.
引用
收藏
页码:269 / 274
页数:6
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