Hubbard J W, Cox R H, Sanders B J, Lawler J E
Neuropharmacology. 1986 Sep;25(9):963-72. doi: 10.1016/0028-3908(86)90189-9.
Studies from this laboratory have shown that the first filial offspring of female spontaneously-hypertensive rats and male Wistar-Kyoto (WKY) normotensive rats develop stress-induced hypertension. The present study sought to examine the effects of intracerebroventricular administration of clonidine (8 micrograms) on cardiovascular and sympathoadrenal responses to aversive classical conditioning in these borderline hypertensive rats (BHR) and in normotensive WKY control rats. Clonidine caused significant reductions in resting arterial pressure, vascular resistance, heart rate and concentrations of epinephrine (E) in plasma for both hypertensive and normotensive rats. Central administration of normal saline to control rats of each strain did not alter basal cardiovascular or sympathoadrenal function. The presentation of a conditioned stimulus (CS) elicited a significant increase in arterial pressure and total peripheral resistance in hypertensive rats treated with saline and clonidine and in normotensive rats treated with saline. In contrast, normotensive rats treated with clonidine showed no increases in arterial pressure or vascular resistance following the onset of the conditioned stimulus. The aversive conditioning session instigated significant increases in the concentrations of norepinephrine (NE) and E in plasma in saline-treated rats. Hypertensive and normotensive rats treated with clonidine-showed a blunted increase in plasma concentrations of NE and E during this period; however, concentrations of E in hypertensive rats increased significantly from the baseline period after injection. These data suggest that an abnormality in central alpha 2-adrenoceptor-mediated inhibition of sympathoadrenal discharge and sympathetic vasomotor tone may predispose the hypertensive rat to develop stress-induced hypertension.
本实验室的研究表明，雌性自发性高血压大鼠与雄性Wistar-Kyoto（WKY）正常血压大鼠的第一代子代会出现应激诱导的高血压。本研究旨在检测向脑室内注射可乐定（8微克）对这些临界高血压大鼠（BHR）和正常血压的WKY对照大鼠在厌恶经典条件反射时心血管和交感肾上腺反应的影响。可乐定可使高血压和正常血压大鼠的静息动脉压、血管阻力、心率以及血浆肾上腺素（E）浓度显著降低。向各品系对照大鼠中枢给予生理盐水并未改变基础心血管或交感肾上腺功能。条件刺激（CS）的呈现使给予生理盐水和可乐定的高血压大鼠以及给予生理盐水的正常血压大鼠的动脉压和总外周阻力显著升高。相比之下，给予可乐定的正常血压大鼠在条件刺激开始后动脉压或血管阻力并未升高。厌恶条件反射过程促使给予生理盐水的大鼠血浆去甲肾上腺素（NE）和E浓度显著升高。在此期间，给予可乐定的高血压和正常血压大鼠血浆NE和E浓度升高减弱；然而，高血压大鼠注射后E浓度较基线期显著升高。这些数据表明，中枢α2-肾上腺素能受体介导的对交感肾上腺释放和交感血管运动张力的抑制异常可能使高血压大鼠易患应激诱导的高血压。
