Li M, Martin A, Liu D T, Whitworth J A
Department of Medicine, St George Hospital, University of New South Wales, Australia.
J Hypertens. 1994 May;12(5):569-76.
An increase in digitalis-like substances has been reported in deoxycorticosterone acetate (DOCA)-salt hypertensive rats. We hypothesized that the role of saline and unilateral nephrectomy in DOCA hypertension may be due to stimulation of endogenous digitalis-like substances.
We investigated the effects of digoxin and DOCA alone and in combination in intact rats drinking water. Forty male Sprague-Dawley rats were used (body weight 223-298 g).
Neither digoxin (40 micrograms/kg per day, by gavage, for 35 days, n = 10) nor DOCA (30 mg/kg twice a week, subcutaneously, for 5 weeks, n = 10) caused a consistent increase in blood pressure in intact rats drinking water. In contrast, combined digoxin and DOCA administration (n = 10) increased systolic blood pressure from day 18 of treatment onwards, to a maximum at day 34 compared with sham-treated rats (n = 10). There were no consistent changes in water intake, urine volume, urinary sodium or potassium excretion, or plasma sodium or potassium concentration with digoxin treatment. DOCA increased water intake and urine volume, and caused an initial decrease in urinary sodium excretion, but no change in urinary potassium excretion or plasma sodium concentration. Plasma potassium excretion was lower in DOCA- than sham-treated rats.
Combined digoxin and DOCA administration in intact rats drinking water increased blood pressure significantly compared with either drug alone, raising the possibility that the mechanism by which nephrectomy and salt loading contribute to DOCA hypertension in the rat might be through stimulation of endogenous digitalis-like substances.
据报道，醋酸脱氧皮质酮（DOCA）-盐性高血压大鼠体内洋地黄样物质增加。我们推测，生理盐水和单侧肾切除在DOCA高血压中的作用可能是由于内源性洋地黄样物质受到刺激。
我们研究了地高辛和DOCA单独及联合使用对饮用自来水的完整大鼠的影响。使用了40只雄性Sprague-Dawley大鼠（体重223 - 298克）。
地高辛（每天40微克/千克，灌胃，持续35天，n = 10）和DOCA（每周两次，每次30毫克/千克，皮下注射，持续5周，n = 10）均未使饮用自来水的完整大鼠血压持续升高。相比之下，联合给予地高辛和DOCA（n = 10）从治疗第18天起收缩压升高，与假手术组大鼠（n = 10）相比，在第34天达到最高值。地高辛治疗对水摄入量、尿量、尿钠或钾排泄以及血浆钠或钾浓度没有持续一致的影响。DOCA增加了水摄入量和尿量，并使尿钠排泄最初减少，但尿钾排泄和血浆钠浓度没有变化。DOCA处理组大鼠的血浆钾排泄低于假手术组大鼠。
与单独使用任何一种药物相比，联合给予地高辛和DOCA可使饮用自来水的完整大鼠血压显著升高，这增加了肾切除和盐负荷导致大鼠DOCA高血压的机制可能是通过刺激内源性洋地黄样物质的可能性。
