Averill D B, Matsumura K, Ganten D, Ferrario C M
Hypertension Center, Division of Surgical Sciences, The Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, NC 27157-1032, USA.
Hypertension. 1996 Mar;27(3 Pt 2):591-7. doi: 10.1161/01.hyp.27.3.591.
Transgenic [Tg(+)] rats carrying the mouse Ren-2d gene [(mRen-2d)27] are a newly established monogenetic form of experimental hypertension. To determine whether the area postrema contributes to the development of hypertension in mRen-2 Tg(+) rats, this circumventricular organ in the fourth ventricle was removed from 5-week-old Tg(+) rats. From weeks 4 through 9, systolic blood pressure was measured weekly by tail-cuff plethysmography in area postrema-lesioned and sham-lesioned Tg(+) rats. Although systolic blood pressure rose markedly in sham-lesioned Tg(+) rats, the increase in systolic blood pressure was significantly attenuated in area postrema-lesioned Tg(+) rats. At 9 weeks of age, a femoral artery was cannulated for the measurement of arterial pressure in awake rats. Mean arterial pressure (MAP) in area postrema-lesioned Tg(+) rats was significantly (P < .01) lower than that in sham-lesioned rats: 171 +/- 7 and 132.+/- 5 mm Hg, respectively. Baroreceptor reflex was evaluated by intravenous infusion of sodium nitroprusside. There was no significant difference in baroreceptor reflex sensitivity between the two groups. Intravenous pentolinium (5 mg/kg), used to produce sympathetic ganglionic block, caused significant decreases in MAP in both groups. However, the reduction of MAP in the sham-lesioned group was significantly (P < .05) greater than that in the area postrema-lesioned group: -73 +/- 4 and -48 +/- 6 mm Hg, respectively. The ratio of left ventricular weight to body weight in sham-lesioned Tg(+) rats was significantly larger than that of area postrema-lesioned rats. These results suggest that ablation of the area postrema markedly attenuates the development of hypertension in mRen-2d Tg(+) rats, and this attenuation may be attributed to decrease in sympathetic outflow.
携带小鼠Ren-2d基因[(mRen-2d)27]的转基因[Tg(+)]大鼠是一种新建立的单基因形式的实验性高血压模型。为了确定最后区是否参与mRen-2 Tg(+)大鼠高血压的发生发展，将5周龄Tg(+)大鼠第四脑室内的这个室周器官切除。在第4至9周，通过尾套体积描记法每周测量最后区损伤和假手术损伤的Tg(+)大鼠的收缩压。虽然假手术损伤的Tg(+)大鼠收缩压显著升高，但最后区损伤的Tg(+)大鼠收缩压的升高明显减弱。在9周龄时，插入股动脉以测量清醒大鼠的动脉压。最后区损伤的Tg(+)大鼠的平均动脉压(MAP)显著(P <.01)低于假手术损伤大鼠：分别为171±7和132±5 mmHg。通过静脉输注硝普钠评估压力感受器反射。两组之间的压力感受器反射敏感性没有显著差异。用于产生交感神经节阻滞的静脉注射潘托铵(5 mg/kg)使两组的MAP均显著降低。然而，假手术损伤组MAP的降低显著(P <.05)大于最后区损伤组：分别为-73±4和-48±6 mmHg。假手术损伤的Tg(+)大鼠左心室重量与体重的比值显著大于最后区损伤大鼠。这些结果表明，切除最后区可显著减弱mRen-2d Tg(+)大鼠高血压的发展，这种减弱可能归因于交感神经传出减少。
