Oliveira-Pelegrin Gabriela Ravanelli, de Azevedo Sergio Vicente, Yao Song Tieng, Murphy David, Rocha Maria José Alves
Departamento de Morfologia, Estomatologia e Fisiologia, Faculdade de Odontologia de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brazil.
J Neuroimmunol. 2010 Oct 8;227(1-2):80-6. doi: 10.1016/j.jneuroim.2010.06.019. Epub 2010 Jul 18.
Our aim was to investigate the effect of central NOS inhibition on hypothalamic arginine vasopressin (AVP) gene expression, hormone release and on the cardiovascular response during experimental sepsis. Male Wistar rats were intracerebroventricularly injected with the non-selective NO synthase (NOS) inhibitor (L-NAME) or aminoguanidine, a selective inhibitor of the inducible isoform (iNOS). After 30 min, sepsis was induced by cecal ligation and puncture (CLP) causing an increase in heart rate (HR), as well as a reduction in median arterial pressure (MAP) and AVP expression ratio (AVP(R)), mainly in the supraoptic nucleus. AVP plasma levels (AVPp) increased in the early but not in the late phase of sepsis. L-NAME pretreatment increased MAP but did not change HR. It also resulted in an increase in AVPp at all time points, except 24h, when it returned to basal levels. AVP(R), however remained reduced in both nuclei. Aminoguanidine pretreatment resulted in increased MAP in the early phase and higher AVP(R) in the supraoptic, but not in the paraventricular nucleus, while AVPp remained elevated at all time points. We suggest that increased central NO production, mainly inducible NOS-derived, reduces AVP gene expression differentially in supraoptic and paraventricular nuclei, and that this may contribute to low AVP plasma levels and hypotension in the late phase of sepsis.
我们的目的是研究中枢一氧化氮合酶（NOS）抑制对实验性脓毒症期间下丘脑精氨酸加压素（AVP）基因表达、激素释放及心血管反应的影响。雄性Wistar大鼠经脑室内注射非选择性NO合酶（NOS）抑制剂（L-NAME）或诱导型异构体（iNOS）的选择性抑制剂氨基胍。30分钟后，通过盲肠结扎和穿刺（CLP）诱导脓毒症，导致心率（HR）增加，以及平均动脉压（MAP）和AVP表达率（AVP(R)）降低，主要发生在视上核。脓毒症早期AVP血浆水平（AVPp）升高，但后期未升高。L- NAME预处理可提高MAP，但不改变HR。除24小时时恢复至基础水平外，L-NAME预处理还导致所有时间点的AVPp均升高。然而，两个核中的AVP(R)仍降低。氨基胍预处理导致早期MAP升高，视上核而非室旁核中的AVP(R)升高，而AVPp在所有时间点均保持升高。我们认为，主要由诱导型NOS产生的中枢NO增加，会对视上核和室旁核中的AVP基因表达产生不同影响，这可能导致脓毒症后期AVP血浆水平降低和低血压。
