Cudd T A
Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station 77843-4466, USA.
Am J Physiol. 1998 May;274(5):R1353-60. doi: 10.1152/ajpregu.1998.274.5.R1353.
Conditions that increase the formation of thromboxane A2 (TxA2) also result in activation of hemodynamic and adrenocortical responses. The purpose of this study was to test the hypothesis that TxA2 acts directly on the brain to mediate these responses. Adult sheep were chronically instrumented with vascular and intracerebroventricular catheters. The TxA2 analog U-46619 (0, 100, or 1,000 ng.kg-1.min-1) and artificial cerebrospinal fluid (CSF) were infused intracerebroventricularly for 30 min. Heart rate increased in response to 100 ng.kg-1.min-1 U-46619 infusions. Heart rate did not change over preinfusion values in response to the highest infusion rate, but values were elevated compared with the postinfusion period. Mean arterial pressure, ACTH, cortisol, hematocrit, and arterial pH (pHa) increased, and arterial partial CO2 pressure (PaCO2) fell in response to 1,000 ng.kg-1.min-1 infusions of U-46619. Plasma vasopressin concentrations and arterial partial O2 pressure did not change. In a second study, U-46619 or artificial CSF was infused intracerebroventricularly during prostaglandin synthase blockade. Blockade reduced but did not prevent blood pressure responses to U-46619 infusion, suggesting that the U-46619 infusions increased prostaglandin synthase metabolism to contribute de novo TxA2 or a second metabolite to augment the blood pressure response. Heart rate, pHa, PaCO2, ACTH, and cortisol responses to U-46619 were not different with blockade. We conclude that TxA2 acts on the brain to mediate blood pressure, heart rate, pHa, PaCO2, hematocrit, ACTH, and cortisol responses. These findings support the hypothesis that TxA2 acts directly on the brain to promote cardiovascular and hormonal responses that may serve a protective function during conditions when TxA2 formation is increased.
增加血栓素A2（TxA2）形成的情况也会导致血流动力学和肾上腺皮质反应的激活。本研究的目的是检验TxA2直接作用于大脑以介导这些反应的假说。成年绵羊长期植入血管和脑室内导管。将TxA2类似物U - 46619（0、100或1000 ng·kg-1·min-1）和人工脑脊液（CSF）脑室内输注30分钟。输注100 ng·kg-1·min-1 U - 46619时心率增加。对最高输注速率，心率相对于输注前值无变化，但与输注后阶段相比有所升高。输注1000 ng·kg-1·min-1 U - 46619时，平均动脉压、促肾上腺皮质激素、皮质醇、血细胞比容和动脉血pH（pHa）升高，动脉血二氧化碳分压（PaCO2）下降。血浆血管加压素浓度和动脉血氧分压未变化。在第二项研究中，在前列腺素合酶阻断期间脑室内输注U - 46619或人工脑脊液。阻断减少但未阻止对U - 46619输注的血压反应，提示U - 46619输注增加了前列腺素合酶代谢，以产生新的TxA2或第二种代谢产物来增强血压反应。阻断时对U - 46619的心率、pHa、PaCO2、促肾上腺皮质激素和皮质醇反应无差异。我们得出结论，TxA2作用于大脑以介导血压、心率、pHa、PaCO2、血细胞比容、促肾上腺皮质激素和皮质醇反应。这些发现支持TxA2直接作用于大脑以促进心血管和激素反应的假说，这些反应在TxA2形成增加的情况下可能起到保护作用。
