Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo (USP), Ribeirão Preto, SP, 14090-900, Brazil.
Pharmaceutical Sciences, Food and Nutrition College, Federal Univesity of Mato Grosso do Sul, UFMS, Campo Grande, MS, Brazil.
Pflugers Arch. 2021 Apr;473(4):697-709. doi: 10.1007/s00424-020-02512-z. Epub 2021 Apr 11.
Ventral medial prefrontal cortex (vMPFC) glutamatergic neurotransmission has a facilitatory role on cardiac baroreflex activity which is mediated by NMDA receptors activation. Corticotrophin releasing factor receptors type1 and 2 (CRF1 and CRF2), present in the vMPFC, are colocalized in neurons containing glutamate vesicles, suggesting that such receptors may be involved in glutamate release in this cortical area. Therefore, our hypothesis is that the CRF1 and CRF2 receptors can modulate the baroreflex bradycardic and tachycardic responses. In order to prove this assumption, male Wistar rats had bilateral stainless steel guide cannula implanted into the vMPFC, and baroreflex was activated by intravenous infusion of phenylephrine or sodium nitroprusside through a vein catheter. A second catheter was implanted into the femoral artery for cardiovascular measurements. The CRF1 receptor antagonist administration in either infralimbic cortex (IL) or prelimbic cortex (PL), vMPFC regions, was unable to change the bradycardic responses but increased the slope of the baroreflex tachycardic activity. Microinjection of the CRF2 receptor antagonist into the IL and PL did not alter ether bradycardic nor tachycardic baroreflex responses. The administration of the non-selective CRF receptors agonist, urocortin in these areas, did not modify bradycardic responses but decreased tachycardia slope of the baroreflex. CRF1 receptor antagonist administration prior to non-selective CRF agonist in vMPFC prevented the tachycardic responses reduction. However, CRF2 receptor antagonism could not prevent the effect of CRF receptors agonist. These results suggest that IL and PL CRF1 but not CRF2 receptors have an inhibitory role on the baroreflex tachycardic activity. Furthermore, they have no influence on baroreflex bradycardic activity.
腹内侧前额皮质(vMPFC)谷氨酸能神经传递对心脏压力反射活动具有促进作用,这种作用是通过 NMDA 受体的激活介导的。存在于 vMPFC 中的促肾上腺皮质释放因子受体 1 型和 2 型(CRF1 和 CRF2)与含有谷氨酸囊泡的神经元共定位,表明这些受体可能参与该皮质区域的谷氨酸释放。因此,我们的假设是 CRF1 和 CRF2 受体可以调节压力反射的心动过缓和心动过速反应。为了证明这一假设,雄性 Wistar 大鼠双侧不锈钢引导套管植入 vMPFC,通过静脉内输注苯肾上腺素或硝普钠通过静脉导管激活压力反射,股动脉内植入第二根导管进行心血管测量。CRF1 受体拮抗剂在扣带回下皮质(IL)或额前皮质(PL)、vMPFC 区域的给药均不能改变心动过缓反应,但增加了压力反射心动过速活动的斜率。CRF2 受体拮抗剂在 IL 和 PL 中的微注射并未改变醚心动过缓和心动过速压力反射反应。在这些区域给予非选择性 CRF 受体激动剂尿皮质素并没有改变心动过缓反应,但降低了压力反射的心动过速斜率。在 vMPFC 中给予非选择性 CRF 激动剂之前给予 CRF1 受体拮抗剂可防止心动过速反应的减少。然而,CRF2 受体拮抗作用不能防止 CRF 受体激动剂的作用。这些结果表明,IL 和 PL 的 CRF1 受体而非 CRF2 受体对压力反射性心动过速活动具有抑制作用。此外,它们对压力反射性心动过缓活动没有影响。