Luo Min, Hess Margaret C, Fink Gregory D, Olson L Karl, Rogers Jennifer, Kreulen David L, Dai Xiaoling, Galligan James J
The Neuroscience Program, Michigan State University, East Lansing, MI 48824, USA.
Auton Neurosci. 2003 Feb 28;104(1):47-57. doi: 10.1016/S1566-0702(02)00287-4.
Sympathetic control of arteries and veins may be altered in hypertension. To test this hypothesis, constrictions of mesenteric arteries and veins caused by nerve stimulation and by norepinephrine (NE) and ATP were studied in vitro in tissues from deoxycorticosterone acetate (DOCA)-salt hypertensive and sham normotensive rats. In DOCA-salt arteries, the maximum neurogenic response was greater than that in sham arteries. The P2 receptor antagonist, pyridoxal-phosphate-6-azophenyl-2',4'-disulfonic acid (PPADS, 10 microM), greatly reduced neurogenic responses in sham but not DOCA-salt arteries. The alpha1-adrenergic receptor antagonist, prazosin (0.1 microM), inhibited responses in DOCA-salt but not sham arteries. Concentration-response curves for norepinephrine and ATP were similar in sham and DOCA-salt arteries, indicating that reactivity to sympathetic vasoconstrictor transmitters was not changed in DOCA-salt arteries. Neurogenic constrictions in sham and DOCA-salt veins were similar in amplitude, and they were completely blocked by prazosin. However, concentration-response curves for norepinephrine in DOCA-salt veins were right-shifted compared to those in sham veins. Cocaine (10 microM) and corticosterone (10 microM) caused a leftward shift in norepinephrine concentration-response curves in DOCA-salt but not sham veins. Norepinephrine content was decreased in DOCA-salt arteries and veins, and there was an increased norepinephrine transporter (NET) level in DOCA-salt veins. These data indicate that, in DOCA-salt hypertension, there is an increased norepinephrine release from sympathetic nerves associated with mesenteric arteries and veins. In arteries, this results in an increase in the amplitude of neurogenic constrictions. In veins, increased norepinephrine release maintains neurogenic constrictions in the presence of increased NET levels.
高血压时动脉和静脉的交感神经控制可能会发生改变。为了验证这一假设,在体外研究了去氧皮质酮醋酸盐(DOCA)-盐性高血压大鼠和假手术正常血压大鼠组织中神经刺激、去甲肾上腺素(NE)和三磷酸腺苷(ATP)引起的肠系膜动脉和静脉收缩情况。在DOCA-盐性动脉中,最大神经源性反应大于假手术动脉。P2受体拮抗剂磷酸吡哆醛-6-偶氮苯-2',4'-二磺酸(PPADS,10微摩尔)可显著降低假手术动脉而非DOCA-盐性动脉的神经源性反应。α1肾上腺素能受体拮抗剂哌唑嗪(0.1微摩尔)可抑制DOCA-盐性动脉而非假手术动脉的反应。假手术动脉和DOCA-盐性动脉中去甲肾上腺素和ATP的浓度-反应曲线相似,表明DOCA-盐性动脉对交感缩血管递质的反应性未改变。假手术静脉和DOCA-盐性静脉的神经源性收缩幅度相似,且均被哌唑嗪完全阻断。然而,与假手术静脉相比,DOCA-盐性静脉中去甲肾上腺素的浓度-反应曲线右移。可卡因(10微摩尔)和皮质酮(10微摩尔)使DOCA-盐性静脉而非假手术静脉的去甲肾上腺素浓度-反应曲线左移。DOCA-盐性动脉和静脉中的去甲肾上腺素含量降低,且DOCA-盐性静脉中去甲肾上腺素转运体(NET)水平升高。这些数据表明,在DOCA-盐性高血压中,与肠系膜动脉和静脉相关的交感神经去甲肾上腺素释放增加。在动脉中,这导致神经源性收缩幅度增加。在静脉中,去甲肾上腺素释放增加在NET水平升高的情况下维持神经源性收缩。