THE ROLE OF NITRIC-OXIDE IN OPIOID-INDUCED PIAL ARTERY VASODILATION
THE ROLE OF NITRIC-OXIDE IN OPIOID-INDUCED PIAL ARTERY VASODILATION
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DOI：
10.1016/0006-8993(95)00081-z
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发表时间：
1995-03-27
期刊：
影响因子：
2.9
通讯作者：
ARMSTEAD, WM
中科院分区：
文献类型：
--
作者：
DEVINE, JO;ARMSTEAD, WM
The present study was designed to investigate the role of nitric oxide (NO) and the production of cGMP in the vasodilator response to opioid agonists in newborn pigs equipped with a closed cranial window. Methionine-enkephalin (10(-8), 10(-6) M), an endogenous mu opioid agonist, produced pial artery dilation that was attenuated by L-nitroarginine (LNA, 10(-6) M), an NO synthase inhibitor (10 +/- 1 vs. 4 +/- 1 and 16 +/- 1 vs. 7 +/- 1% for 10(-8), 10(-6) M methionine-enkephalin, respectively). Methionine-enkephalin-induced vasodilation was associated with increased cortical periarachnoid CSF cGMP and these changes in CSF cGMP were attenuated by LNA (354 +/- 11 and 596 +/- 32 vs. 278 +/- 13 and 266 +/- 19 fmol/ml for control and methionine-enkephalin 10(-6) M before and after LNA, respectively). Leucine enkephalin, an endogenous delta agonist, elicited similar changes in pial diameter and CSF cGMP while dynorphin, an endogenus k agonist, produced dilation associated with large increases in CSF cGMP (374 +/- 18 vs. 1054 +/- 45 fmol/ml for central and dynorphin 10(-6) M, respectively). Vascular and biochemical changes for these two opioids were similarly attenuated by LNA. The synthetic selective opioid receptor agonists, DAMGO, DPDPE, deltorphin, and U50,488H (10(-8), 10(-6) M) mu, delta(1), delta(2), and kappa agonists, respectively also elicited increases in pial artery diameter and CSF cGMP that were similarly attenuated by LNA. The coadministration of L-Arg (10(-3) M) with LNA partially restored opioid-induced pial artery dilation and associated changes in CSF cGMP whereas D-Arg (10(-3) M) coadministered with LNA did not restore opioid-induced vascular and biochemical changes. These data indicate that NO contributes to opioid-mediated pial artery vasodilation.
