L-NAME, NITRIC-OXIDE AND JEJUNAL MOTILITY, BLOOD-FLOW AND OXYGEN-UPTAKE IN DOGS

被引:24
作者
ALEMAYEHU, A
LOCK, KR
COATNEY, RW
CHOU, CC
机构
[1] MICHIGAN STATE UNIV,DEPT PHYSIOL,E LANSING,MI 48824
[2] MICHIGAN STATE UNIV,DEPT MED,E LANSING,MI 48824
关键词
INTESTINAL MOTILITY; INTESTINAL BLOOD FLOW; INTESTINAL OXYGEN CONSUMPTION; NITRIC OXIDE; L-NAME; L-ARGININE; D-ARGININE; NITROGLYCERIN; ENTERIC NERVOUS SYSTEM;
D O I
10.1111/j.1476-5381.1994.tb14045.x
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
1 The effects of the inhibitor of nitric oxide (NO) synthesis, N-G-nitro-L-arginine methyl ester (L-NAME), on systemic arterial blood pressure and jejunal motility, blood flow, and oxygen uptake have been investigated in anaesthetized dogs. 2 L-NAME (cumulative doses of 0.1-20 mg kg(-1), i.v.) dose-dependently increased blood pressure and jejunal motility and decreased heart rate. The maximal response of these three variables occurred at doses, 3, 10 and 10 mg kg(-1), respectively. L-NAME (cumulative doses of 0.5-5 mg kg(-1)) also dose-dependently induced jejunal vasoconstriction. The jejunal vascular resistance returned to control values as the cumulative doses reached 10 and 20 mg kg(-1), which corresponded to the maximal increase in jejunal motility. 3 A single intravenous injection of L-NAME (10 mg kg(-1)) produced a prompt increase in blood pressure, which lasted for at least 50 min. 4 L-NAME (10 mg kg(-1)) produced a progressive rise in jejunal motility reaching its maximum (47 +/- 6 mmHg) 15 min after the administration, and lasting for 40-50 min. Both the basal lumen pressure and the amplitude of rhythmic contractions increased during this period. 5 L-NAME (10 mg kg(-1)) produced a triphasic change in jejunal vascular resistance and blood flow measured by timed collection of venous outflow. The blood flow decreased initially (-43% at 5 min), increased (+35%) and returned to control value between 15 and 35 min, then decreased (-35%) 40-50 min post-infusion. Jejunal vascular resistance reflected the blood flow response (+88% at both 5 and 50 min). The time during which the reversal of the vasoconstriction occurred (15-35 min) corresponded to the time of marked increase in motility, and was accompanied by a significant increase in jejunal oxygen uptake (+18%). 6 The L-NAME-induced increase in motility was prevented by L-arginine (1 g kg(-1), i.v.) but not by D-arginine pretreatment. The interim (15-35 min) changes in jejunal blood flow, vascular resistance and oxygen uptake were also prevented by L-arginine pretreatment. 7 L-Arginine pretreatment attenuated L-NAME-induced hypertension for 5 min. 8 The L-NAME-induced increases in jejunal vascular resistance and motility were inhibited by either local intra-arterial infusion of L-arginine (32 mM local arterial blood concentration) or topical application of 2 mu M nitroglycerin. Infusion of D-arginine (32 mM local arterial blood concentration) had no such effect. 9 The L-NAME-induced increase in blood pressure was not the mechanism by which jejunal motility was increased, because similar increases in blood pressure by mefenamate (10 mg kg(-1), i.v.) had no such effect. 10 Thus, inhibition of nitric oxide synthesis by L-NAME increased jejunal motility and vascular resistance and the marked increase in motility can abolish or reverse the vasoconstriction. Endogenous nitric oxide may play a role in regulating motility and blood flow in the resting canine jejunum.
引用
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页码:205 / 212
页数:8
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