Mao H Z, Li Z, Chapleau M W
Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52242, USA.
Hypertension. 1996 Mar;27(3 Pt 2):584-90. doi: 10.1161/01.hyp.27.3.584.
The carotid sinuses, one of the major sites of baroreceptor innervation, are also a common site of atherosclerotic lesions and platelet aggregation. The goal of the present study was to determine whether platelet activation in carotid sinuses causes reflex-mediated changes in renal sympathetic nerve activity and arterial pressure. Rabbit platelets were isolated, resuspended in Krebs' buffer, and activated by thrombin. Injection of activated platelets (3 x 10(8) platelets/mL) into the vascularly isolated carotid sinuses of anesthetized rabbits essentially eliminated sympathetic nerve activity and acutely decreased mean arterial pressure from 126 +/- 5 to 53 +/- 4 mm Hg (n=16; P < .05). Sympathetic activity and arterial pressure returned to control levels over a period of minutes despite sustained exposure to activated platelets. Injection of U-46619, a thromboxane analogue and vasoconstrictor, into carotid sinuses did not alter sympathetic activity or arterial pressure. However, serotonin (5-hydroxytryptamine [5-HT]), which is known to be released from activated platelets, and the 5-HT3 receptor agonist phenylbiguanide mimicked the effect of platelets. Furthermore, the platelet-induced reflex inhibition of sympathetic activity and hypotension were not altered by the cyclooxygenase inhibitor indomethacin but were attenuated significantly by 5-HT receptor antagonists. Platelet activation inhibited sympathetic activity to 5 +/- 2% of control in the absence of antagonists but to only 35 +/- 11 and 76 +/- 4% of control after selective blockade of 5-HT2 and 5-HT3 receptors with ketanserin and MDL-72222, respectively. The results indicate that (1) platelet activation in carotid sinuses triggers reflex inhibition of sympathetic nerve activity and hypotension; (2) the reflex is not caused by carotid vasoconstriction and is not mediated by prostanoids; and (3) the reflex is mediated by 5-HT acting primarily on 5-HT3 and to a lesser extent on 5-HT2 receptors. We speculate that this reflex may contribute to arterial pressure lability and susceptibility to stroke in patients with carotid atherosclerotic disease.
颈动脉窦是压力感受器神经支配的主要部位之一，也是动脉粥样硬化病变和血小板聚集的常见部位。本研究的目的是确定颈动脉窦内的血小板激活是否会引起反射介导的肾交感神经活动和动脉血压变化。分离兔血小板，重悬于 Krebs 缓冲液中，并用凝血酶激活。将激活的血小板（3×10⁸ 个血小板/mL）注入麻醉兔的血管分离的颈动脉窦，基本上消除了交感神经活动，并使平均动脉压从 126±5 毫米汞柱急剧降至 53±4 毫米汞柱（n = 16；P <.05）。尽管持续暴露于激活的血小板，但交感神经活动和动脉血压在几分钟内恢复到对照水平。将血栓素类似物和血管收缩剂 U - 46619 注入颈动脉窦，并未改变交感神经活动或动脉血压。然而，已知从激活的血小板中释放的血清素（5 - 羟色胺[5 - HT]）和 5 - HT3 受体激动剂苯乙双胍模拟了血小板的作用。此外，血小板诱导的交感神经活动反射抑制和低血压不受环氧化酶抑制剂吲哚美辛的影响，但被 5 - HT 受体拮抗剂显著减弱。在没有拮抗剂的情况下，血小板激活将交感神经活动抑制至对照的 5±2%，但在用酮色林和 MDL - 72222 分别选择性阻断 5 - HT2 和 5 - HT3 受体后，仅抑制至对照的 35±11%和 76±4%。结果表明：（1）颈动脉窦内的血小板激活触发交感神经活动的反射抑制和低血压；（2）该反射不是由颈动脉血管收缩引起的，也不由前列腺素介导；（3）该反射由 5 - HT 介导，主要作用于 5 - HT3 受体，对 5 - HT2 受体的作用较小。我们推测这种反射可能导致颈动脉粥样硬化疾病患者的动脉血压不稳定和中风易感性。
