Li P, Morris M, Ferrario C M, Barrett C, Ganten D, Callahan M F
Department of Physiology and Pharmacology and The Hypertension Center, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157-1083, USA.
Am J Physiol. 1998 Oct;275(4):H1130-7. doi: 10.1152/ajpheart.1998.275.4.H1130.
We previously demonstrated that mRen-2 transgenic [Tg(+)] rats are sensitive to chronic high NaCl intake, showing increased arterial pressure and vasopressin (VP) secretion. In this study, we determined the effect of a chronic osmotic challenge, 4 days of drinking 2% NaCl, on direct arterial blood pressure, heart rate, fluid-electrolyte balance, circadian rhythm of mean arterial pressure (MAP), and changes in plasma VP and catecholamines. Under baseline conditions, male Tg(+) rats showed a significant shift in the peak in circadian MAP into the light portion of the day-night cycle. Substitution of 2% NaCl for drinking water caused a rapid increase in MAP, 20 +/- 5 mmHg in Tg(+) rats within 6 h. Whereas the amplitude of circadian MAP fluctuations increased in salt-loaded Tg(+) rats, there was no significant change in the circadian timing of peak MAP with salt loading. Tg(+) rats showed exaggerated osmotic-induced increases in plasma VP, norepinephrine (NE), and epinephrine (Epi) compared with Tg(-) rats. Plasma NE and Epi were increased two- and fourfold, respectively, in the hypertensive rats with no significant change in the Tg(-) rats. Intravenous administration of a VP antagonist did not alter arterial pressure in either Tg(+) or Tg(-) rats. Tg(+) and Tg(-) rats showed a positive sodium balance with no significant difference observed between the groups. Tg(+) rats showed a significant increase in salt consumption, plasma sodium, osmolality, and hematocrit, accompanied by a negative water balance. We conclude that Tg(+) rats are sensitive to acute and chronic osmotic stimuli in terms of blood pressure, fluid-electrolyte balance, and plasma VP and catecholamines. Whereas elevated plasma VP does not contribute to the hypertensive response, increased sympathetic drive may mediate the salt-induced blood pressure changes in this model.
我们之前证明，mRen-2转基因[Tg(+)]大鼠对慢性高盐摄入敏感，表现为动脉血压升高和血管加压素（VP）分泌增加。在本研究中，我们测定了慢性渗透刺激（饮用2% NaCl 4天）对直接动脉血压、心率、液体电解质平衡、平均动脉压（MAP）的昼夜节律以及血浆VP和儿茶酚胺变化的影响。在基线条件下，雄性Tg(+)大鼠的昼夜MAP峰值显著移至昼夜周期的光照时段。用2% NaCl替代饮用水导致MAP迅速升高，Tg(+)大鼠在6小时内升高20±5 mmHg。虽然盐负荷的Tg(+)大鼠昼夜MAP波动幅度增加，但盐负荷时MAP峰值的昼夜时间没有显著变化。与Tg(-)大鼠相比，Tg(+)大鼠的血浆VP、去甲肾上腺素（NE）和肾上腺素（Epi）因渗透诱导而升高更为明显。高血压Tg(+)大鼠的血浆NE和Epi分别增加了两倍和四倍，而Tg(-)大鼠无显著变化。静脉注射VP拮抗剂对Tg(+)或Tg(-)大鼠的动脉血压均无影响。Tg(+)和Tg(-)大鼠均表现为钠平衡为正，两组之间无显著差异。Tg(+)大鼠的盐摄入量、血浆钠、渗透压和血细胞比容显著增加，同时伴有水平衡为负。我们得出结论，Tg(+)大鼠在血压、液体电解质平衡以及血浆VP和儿茶酚胺方面对急性和慢性渗透刺激敏感。虽然血浆VP升高对高血压反应无作用，但交感神经驱动增加可能介导了该模型中盐诱导的血压变化。
