López Ruth, Llinás Maria Teresa, Salazar Elena, Salazar F Javier
*Department of Physiology, School of Medicine, Universidad de Murcia; †Regional Campus of International Excellence "Mare Nostrum"; and ‡Instituto Murciano de Investigación Biomédica.
J Cardiovasc Pharmacol. 2015 May;65(5):465-72. doi: 10.1097/FJC.0000000000000215.
The involvement of both cyclooxygenase (COX) isoforms in regulating renal function is well known but their interactions with other regulatory mechanisms, such as angiotensin II (Ang II) and nitric oxide (NO), are not well defined. This study has evaluated the relative contribution of both COX isoforms in regulating renal function when NO synthesis is reduced with and without a simultaneous increment in Ang II levels. The renal responses to a nonselective (meclofenamate) or a selective COX2 (nimesulide) inhibitor were examined in dogs pretreated with L-NAME with or without an intrarenal Ang II infusion. Meclofenamate induced a greater (P < 0.05) renal vasoconstriction than nimesulide in dogs pretreated with L-NAME. This vasoconstriction seems to be Ang II-dependent because it was reduced (P < 0.05) by captopril administration. Meclofenamate also induced a greater (P < 0.05) renal vasoconstriction than that elicited by nimesulide in dogs with reduced NO synthesis and elevated Ang II levels. The renal vasoconstriction induced by nimesulide but not that elicited by meclofenamate in dogs pretreated with L-NAME and Ang II, decreased (P < 0.05) during an extracellular volume expansion. These results demonstrate that the nonselective COX inhibition induces a greater renal vasoconstriction than that elicited by the selective COX2 inhibition when NO synthesis is reduced, and when NO synthesis is reduced and Ang II levels are elevated.
环氧化酶（COX）的两种同工型参与调节肾功能已广为人知，但其与其他调节机制（如血管紧张素II（Ang II）和一氧化氮（NO））的相互作用尚不明确。本研究评估了在NO合成减少且Ang II水平同时升高或未升高的情况下，两种COX同工型在调节肾功能中的相对作用。在用L-NAME预处理且有或无肾内Ang II输注的犬中，检测了对非选择性（甲氯芬那酸）或选择性COX2（尼美舒利）抑制剂的肾反应。在L-NAME预处理的犬中，甲氯芬那酸比尼美舒利诱导出更大程度（P < 0.05）的肾血管收缩。这种血管收缩似乎依赖于Ang II，因为卡托普利给药可使其减轻（P < 0.05）。在NO合成减少且Ang II水平升高的犬中，甲氯芬那酸也比尼美舒利诱导出更大程度（P < 0.05）的肾血管收缩。在L-NAME和Ang II预处理的犬中，尼美舒利诱导的肾血管收缩而非甲氯芬那酸诱导的肾血管收缩，在细胞外液量扩张期间减轻（P < 0.05）。这些结果表明，当NO合成减少时，以及当NO合成减少且Ang II水平升高时，非选择性COX抑制比选择性COX2抑制诱导出更大程度的肾血管收缩。
