Yamada K, Goto A, Nagoshi H, Hui C, Omata M
Division of Health Care, Sanraku Hospital, Tokyo, Japan.
Hypertension. 1994 Jun;23(6 Pt 2):1027-31. doi: 10.1161/01.hyp.23.6.1027.
Intracerebroventricular infusion of artificial sodium-rich cerebrospinal fluid induces increases in blood pressure and urinary sodium excretion. To examine the role of brain ouabainlike compound in these central nervous system-mediated responses, we evaluated the effects of prior intracerebroventricular injection of the Fab fragments of digoxin-specific antibody (Digibind, 10 mg/mL, 10 microL) on changes in blood pressure and urinary sodium excretion after intracerebroventricular infusion of high-sodium (323 mmol/L, 150 microL/kg per 15 minutes) cerebrospinal fluid in anesthetized rats. Antiouabain action of Digibind was revealed by the inhibition of a contractile response to ouabain in guinea pig aorta. Similar significant increases in blood pressure were found in rats that received preinjection of Digibind (n = 14) compared with control rats that received injection of saline (n = 5) or normal sheep IgG (n = 8). In rats pretreated with Digibind the natriuretic responses to central high sodium were significantly diminished by 68% (P < .05) or 82% (P < .05) compared with rats treated with saline or normal IgG, respectively. In contrast, Digibind did not affect either pressor or natriuretic responses to intracerebroventricular angiotensin II (600 ng/30 microL per 10 minutes). These data indicate that Digibind significantly inhibits increases in renal sodium excretion in response to high central sodium and suggest that brain ouabainlike compound may be involved in central nervous system-mediated natriuresis with nonpressor mechanisms.
脑室内注入富含钠的人工脑脊液可导致血压升高和尿钠排泄增加。为了研究脑哇巴因样化合物在这些中枢神经系统介导的反应中的作用，我们评估了预先脑室内注射地高辛特异性抗体的Fab片段（地高辛抗体片段，10 mg/mL，10 μL）对麻醉大鼠脑室内注入高钠（323 mmol/L，每15分钟150 μL/kg）脑脊液后血压和尿钠排泄变化的影响。地高辛抗体片段的抗哇巴因作用通过抑制豚鼠主动脉对哇巴因的收缩反应得以揭示。与接受盐水注射的对照大鼠（n = 5）或正常羊IgG注射的大鼠（n = 8）相比，接受地高辛抗体片段预注射的大鼠（n = 14）血压也出现了类似的显著升高。与分别接受盐水或正常IgG处理的大鼠相比，用地高辛抗体片段预处理的大鼠对中枢高钠的利钠反应分别显著降低了68%（P < 0.05）或82%（P < 0.05）。相比之下，地高辛抗体片段对脑室内注入血管紧张素II（每10分钟600 ng/30 μL）引起的升压或利钠反应均无影响。这些数据表明，地高辛抗体片段可显著抑制对中枢高钠的肾钠排泄增加，并提示脑哇巴因样化合物可能通过非升压机制参与中枢神经系统介导的利钠作用。
