Third Department of Clinical Pharmacy, School of Pharmaceutical Sciences, Kyushu University of Medical Science, Nobeoka, Miyazaki 882-8508, Japan.
Second Department of Pharmacology, School of Pharmaceutical Sciences, Kyushu University of Medical Science, Nobeoka, Miyazaki 882-8508, Japan.
J Smooth Muscle Res. 2024;60:54-63. doi: 10.1540/jsmr.60.54.
Although naloxone is an antagonist of the opioid µ receptor, its effect on the peripheral sympathetic nerve function in the blood vessels has not yet been definitively elucidated. Therefore, we examined the effects of naloxone on vasoconstriction of the vascular smooth muscle of rats. Isolated rat mesenteric vascular-intestinal loop preparations were treated with either endogenous or exogenous α adrenoceptor agonists followed by prazosin, a selective antagonist of the α adrenoceptor, or naloxone, and noradrenaline overflow was measured. Vasoconstriction caused by peri-arterial nerve stimulation (PNS) and phenylephrine, an exogenous agonist of the α adrenoceptor, was abolished by prazosin. However, prazosin did not affect PNS-induced endogenous noradrenaline overflow. Naloxone did not affect either PNS-induced endogenous noradrenaline overflow or vasoconstriction. However, naloxone did inhibit phenylephrine-induced vasoconstriction. In addition, naloxone did not affect the angiotensin II-induced vasoconstriction. These results demonstrate that naloxone selectively inhibits vasoconstriction caused by phenylephrine, but not vasoconstriction caused by endogenous noradrenaline released from sympathetic nerve cells in the rat mesenteric vasculature.
虽然纳洛酮是阿片类药物μ受体的拮抗剂，但它对血管外周交感神经功能的影响尚未明确。因此，我们研究了纳洛酮对大鼠血管平滑肌收缩的影响。用内源性或外源性α肾上腺素能受体激动剂处理分离的大鼠肠系膜血管-肠环制剂，然后用选择性α肾上腺素能受体拮抗剂普萘洛尔或纳洛酮处理，并测量去甲肾上腺素的溢出量。动脉周围神经刺激（PNS）和苯肾上腺素（外源性α肾上腺素能受体激动剂）引起的血管收缩被普萘洛尔消除。然而，普萘洛尔不影响 PNS 诱导的内源性去甲肾上腺素溢出。纳洛酮既不影响 PNS 诱导的内源性去甲肾上腺素溢出，也不影响血管收缩。然而，纳洛酮抑制了苯肾上腺素引起的血管收缩。此外，纳洛酮不影响血管紧张素Ⅱ引起的血管收缩。这些结果表明，纳洛酮选择性抑制苯肾上腺素引起的血管收缩，但不抑制大鼠肠系膜血管交感神经细胞释放的内源性去甲肾上腺素引起的血管收缩。
