Lefèvre-Borg F, Mathias O, Cavero I
Department of Biology, Laboratoires d'Etudes et de Recherches Synthélabo, Paris, France.
Hypertension. 1988 Apr;11(4):360-70. doi: 10.1161/01.hyp.11.4.360.
In conscious spontaneously hypertensive rats (SHR), 2, 3, 6, 9, 12, and 16 months of age, the blockade of autonomic ganglia (with chlorisondamine) or postjunctional alpha 1-adrenergic receptors (with prazosin) or the depletion of peripheral norepinephrine stores (with syrosingopine), in contrast to the blockade of alpha 2-adrenergic receptors (with yohimbine, rauwolscine), produced a sustained decrease in the directly measured mean tail artery blood pressure. In 3- to 9-month-old SHR, the fall in blood pressure after prazosin pretreatment was significantly smaller than that after chlorisondamine or syrosingopine pretreatment. In ganglion-blocked SHR, prazosin decreased blood pressure only when this parameter had been elevated by an intra-arterial infusion of epinephrine or norepinephrine. In contrast, under the same experimental conditions, yohimbine or rauwolscine administration failed to modify the pressor effects of either phenylephrine or epinephrine but partially reduced those of norepinephrine and, unlike prazosin, strongly antagonized those of B-HT 920. In either intact or ganglion-blocked SHR, a 30-minute intra-arterial infusion of diltiazem at 100.0, but not 25.0, micrograms/kg/min significantly decreased baseline mean tail artery blood pressure. In ganglion-blocked SHR, the smaller dose of diltiazem antagonized by 40 and 80% the pressor effects of norepinephrine and B-HT 920, respectively, but failed to change the vasoconstrictor responses of phenylephrine, epinephrine, or vasopressin, which were, however, reduced by the higher dose of diltiazem. These results indicate that, in conscious adult SHR, norepinephrine released by peripheral sympathetic nervous terminals and humorally borne epinephrine stimulate almost exclusively post-junctional alpha 1-adrenergic receptors. The latter findings may account for the lack of blood pressure-lowering effects of the studied calcium antagonists at doses that effectively antagonize alpha 2-adrenergic receptor-mediated vasoconstriction in conscious SHR.
在清醒的自发性高血压大鼠（SHR）中，年龄分别为2、3、6、9、12和16个月，与α2 - 肾上腺素能受体阻断剂（育亨宾、萝芙素）不同，自主神经节阻断剂（樟磺咪芬）、节后α1 - 肾上腺素能受体阻断剂（哌唑嗪）或外周去甲肾上腺素储存耗竭剂（利血平）可使直接测量的平均尾动脉血压持续下降。在3至9个月大的SHR中，哌唑嗪预处理后的血压下降幅度明显小于樟磺咪芬或利血平预处理后的下降幅度。在神经节阻断的SHR中，只有当通过动脉内输注肾上腺素或去甲肾上腺素使该参数升高时，哌唑嗪才会降低血压。相反，在相同实验条件下，给予育亨宾或萝芙素未能改变去氧肾上腺素或肾上腺素的升压作用，但部分降低了去甲肾上腺素的升压作用，并且与哌唑嗪不同，强烈拮抗B - HT 920的升压作用。在完整或神经节阻断的SHR中，以100.0微克/千克/分钟而非25.0微克/千克/分钟的剂量进行30分钟的动脉内输注地尔硫卓可显著降低基线平均尾动脉血压。在神经节阻断的SHR中，较小剂量的地尔硫卓分别使去甲肾上腺素和B - HT 920的升压作用拮抗40%和80%，但未能改变去氧肾上腺素、肾上腺素或血管加压素的血管收缩反应，然而，较高剂量的地尔硫卓可使其降低。这些结果表明，在清醒的成年SHR中，外周交感神经末梢释放的去甲肾上腺素和体液携带的肾上腺素几乎仅刺激节后α1 - 肾上腺素能受体。后一发现可能解释了在清醒SHR中，所研究的钙拮抗剂在有效拮抗α2 - 肾上腺素能受体介导的血管收缩的剂量下无降压作用的原因。
