Vaquero E, Molero X, Puig-Diví V, Malagelada J R
Digestive System Research Unit, Hospital General Universitari Vall d'Hebron, Barcelona, Spain.
Gut. 1998 Nov;43(5):684-91. doi: 10.1136/gut.43.5.684.
Nitric oxide (NO) blockade by L-nitroarginine methyl ester (L-NAME) inhibits pancreatic secretion in vivo and aggravates caerulein induced pancreatitis. Nitric oxide synthase (NOS) is present in pancreatic islets, endothelium, and nerve fibres. L-NAME blocks all known NOS isoforms.
To investigate the source of NO blocked by L-NAME that inhibits amylase secretion.
Amylase output was measured in rats in response to caerulein (0.1-50 microg/kg) alone or with indazole. Baseline secretion and the response to supramaximal caerulein were also examined after administration of indazole, L-NAME, haemoglobin, or aminoguanidine under continuous blood pressure measurement. In separate experiments, pancreatic secretion was measured after blockade of afferent nerve fibres by either systemic or local capsaicin. The effect of neural NOS inhibition on caerulein induced pancreatitis was also investigated.
L-NAME, haemoglobin, and supramaximal caerulein (10 microg/kg) increased blood pressure, whereas indazole and suboptimal caerulein (0.1 microg/kg) did not. Indazole and capsaicin decreased basal amylase output. L-NAME and haemoglobin reduced basal amylase output to a lesser extent and potentiated the inhibitory response to supramaximal caerulein. In contrast, full neural NOS inhibition by L-NAME partially reversed the expected caerulein induced suppression of amylase output. This effect was reproduced by indazole and capsaicin. Indazole did not alter responses to either optimal (0.25 microg/kg) or suboptimal (0.1 microg/kg) caerulein, nor, in contrast with L-NAME, aggravate the outcome of caerulein induced pancreatitis.
Reduction of circulating NO availability, probably of endothelial origin, is responsible for the decrease in amylase secretion observed in the early response to L-NAME. Nitrergic neurotransmission plays an important role in the control of pancreatic secretion and may induce opposite effects to endothelial NOS activity.
L-硝基精氨酸甲酯（L-NAME）对一氧化氮（NO）的阻断作用在体内可抑制胰腺分泌，并加重蛙皮素诱导的胰腺炎。一氧化氮合酶（NOS）存在于胰岛、内皮和神经纤维中。L-NAME可阻断所有已知的NOS亚型。
研究被L-NAME阻断的抑制淀粉酶分泌的NO的来源。
测量大鼠对单独蛙皮素（0.1 - 50微克/千克）或与吲唑联合使用时的淀粉酶分泌量。在持续测量血压的情况下，给予吲唑、L-NAME、血红蛋白或氨基胍后，还检测了基础分泌以及对超最大剂量蛙皮素的反应。在单独的实验中，通过全身或局部辣椒素阻断传入神经纤维后测量胰腺分泌。还研究了神经型NOS抑制对蛙皮素诱导的胰腺炎的影响。
L-NAME、血红蛋白和超最大剂量蛙皮素（10微克/千克）可使血压升高，而吲唑和次最大剂量蛙皮素（0.1微克/千克）则不会。吲唑和辣椒素可降低基础淀粉酶分泌量。L-NAME和血红蛋白在较小程度上降低基础淀粉酶分泌量，并增强对超最大剂量蛙皮素的抑制反应。相比之下，L-NAME对神经型NOS的完全抑制部分逆转了预期的蛙皮素诱导的淀粉酶分泌抑制作用。吲唑和辣椒素也产生了这种效果。吲唑既不改变对最佳剂量（0.25微克/千克）或次最佳剂量（0.1微克/千克）蛙皮素的反应，也不像L-NAME那样加重蛙皮素诱导的胰腺炎的病情。
循环中NO可用性的降低，可能源于内皮细胞，是在对L-NAME的早期反应中观察到的淀粉酶分泌减少的原因。一氧化氮能神经传递在胰腺分泌的控制中起重要作用，并且可能对内皮型NOS活性产生相反的影响。
