Pamnani M B, Chen S, Yuan C M, Haddy F J
Department of Physiology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814-4799.
Hypertension. 1994 Jan;23(1 Suppl):I106-9. doi: 10.1161/01.hyp.23.1_suppl.i106.
Endogenous Na+,K(+)-ATPase inhibitors may have a role in the mechanism of low-renin hypertension. Two such compounds have been characterized: ouabain from human plasma and resibufogenin from toad plasma. Previously, we examined the acute effects of ouabain and bufalin (which has the same structure as resibufogenin except for one H+) in normal rats. Bufalin raised blood pressure, but ouabain had little effect. In contrast, given chronically, ouabain substantially increased blood pressure in normal rats and 70% reduced renal mass rats on a salt-free diet. We have now examined the chronic effects of bufalin in rats. Normal rats received 14.8 micrograms/kg per day bufalin or an equimolar dose of ouabain intraperitoneally for 6 weeks; 70% reduced renal mass rats also received 14.8 micrograms/kg per day bufalin. Another group of normal rats received 29.6 micrograms/kg per day bufalin intraperitoneally for 6 weeks. Respective control animals received vehicle. In contrast to ouabain, blood pressure did not increase in normal rats receiving the 14.8 micrograms dose of bufalin. However, normal rats receiving 29.6 micrograms bufalin and 70% reduced renal mass rats receiving 14.8 micrograms bufalin developed significant increases in blood pressure. Increases in blood pressure were associated with decreases in myocardial Na+,K(+)-ATPase activity and correlated with increased plasma Na+,K(+)-ATPase inhibitory activity. Thus, although bufalin is a more potent pressor agent than ouabain when both agents are given acutely, ouabain is at least as potent a vasopressor agent as bufalin when given chronically. Thus, both are pressor agents, more so in the presence of reduced renal mass, when given chronically in the rat.
内源性钠钾ATP酶抑制剂可能在低肾素性高血压的发病机制中起作用。已鉴定出两种此类化合物：人血浆中的哇巴因和蟾蜍血浆中的脂蟾毒配基。此前，我们研究了哇巴因和蟾毒灵（其结构与脂蟾毒配基相同，只是少一个氢原子）对正常大鼠的急性影响。蟾毒灵可升高血压，但哇巴因几乎没有作用。相比之下，长期给药时，哇巴因可使正常大鼠血压大幅升高，使无盐饮食的肾质量减少70%的大鼠血压升高70%。我们现在研究了蟾毒灵对大鼠的慢性影响。正常大鼠每天腹腔注射14.8微克/千克蟾毒灵或等摩尔剂量的哇巴因，持续6周；肾质量减少70%的大鼠也每天腹腔注射14.8微克/千克蟾毒灵。另一组正常大鼠每天腹腔注射29.6微克/千克蟾毒灵，持续6周。相应的对照动物注射溶剂。与哇巴因不同，接受14.8微克剂量蟾毒灵的正常大鼠血压并未升高。然而，接受29.6微克蟾毒灵的正常大鼠和接受14.8微克蟾毒灵的肾质量减少70%的大鼠血压显著升高。血压升高与心肌钠钾ATP酶活性降低有关，并与血浆钠钾ATP酶抑制活性增加相关。因此，尽管急性给药时蟾毒灵比哇巴因是更强的升压剂，但长期给药时哇巴因作为血管升压剂至少与蟾毒灵一样有效。因此，在大鼠长期给药时，两者都是升压剂，在肾质量减少的情况下更是如此。
