Durakoglugil Murat S, Orer Hakan S
Department of Pharmacology, Faculty of Medicine, Hacettepe University, 06100 Ankara, Turkey.
Int J Biomed Sci. 2008 Sep;4(3):229-37.
The effects of cannabinoids on the baroreflex have been investigated in the nucleus tractus solitarii (NTS). In urethane-anesthetized rats, microinjection of the cannabinoid (CB) receptor agonist WIN 55212-2 (100 mM) into the NTS produced a short lasting decrease in arterial pressure (from 95.2 ± 2.9 to 76.2 ± 1.5, n=5, P<0.05) but no change in the heart rate. Another cannabinoid agonist, CP 55940 (100 mM) also caused hypotensive responses (from 90.2 ± 11.3 to 66.4 ± 12.3 mmHg, n=5, P<0.05). Simultaneous sympathetic nerve discharge recordings showed suppression prior to the arterial pressure lowering effect of these agonists. Microinjection of the cannabinoid receptor antagonist, AM 281 (70 mM) did not cause any significant change in arterial pressure (from 100.8 ± 12 mmHg to 108.1 ± 12.8 mmHg, n=5, P>0.05) though it inhibited the agonist-induced responses. The non-NMDA receptor antagonist, DNQX (4 mM) microinjections antagonized the actions of CB agonist WIN 55212-2. Furthermore, sinoaortic denervation attenuated the responses to CB agonists suggesting an intact baroreflex arc is necessary to elicit CB-mediated effects. Neither WIN 55212-2 nor AM 281, altered baroreceptor reflex activation by bolus phenylephrine (25 microg//kg) injections. These data suggest that cannabinoid receptors in the NTS are not involved in the tonic regulation of the arterial pressure but may have a modulatory role in the baroreceptor reflex integration.
大麻素对压力感受性反射的影响已在孤束核(NTS)中进行了研究。在乌拉坦麻醉的大鼠中,向NTS微量注射大麻素(CB)受体激动剂WIN 55212-2(100 mM)可使动脉血压产生短暂下降(从95.2±2.9降至76.2±1.5,n = 5,P<0.05),但心率无变化。另一种大麻素激动剂CP 55940(100 mM)也引起了降压反应(从90.2±11.3降至66.4±12.3 mmHg,n = 5,P<0.05)。同时记录交感神经放电显示,在这些激动剂降低动脉血压的作用之前,交感神经放电受到抑制。微量注射大麻素受体拮抗剂AM 281(70 mM)虽然抑制了激动剂诱导的反应,但未引起动脉血压的任何显著变化(从100.8±12 mmHg升至108.1±12.8 mmHg,n = 5,P>0.05)。非NMDA受体拮抗剂DNQX(4 mM)微量注射可拮抗CB激动剂WIN 55212-2的作用。此外,去窦主动脉神经减弱了对CB激动剂的反应,表明完整的压力感受性反射弧是引发CB介导效应所必需的。WIN 55212-2和AM 281均未改变大剂量注射去氧肾上腺素(25μg/kg)引起的压力感受器反射激活。这些数据表明,NTS中的大麻素受体不参与动脉血压的紧张性调节,但可能在压力感受器反射整合中具有调节作用。