EFFECTS OF OUABAIN ON VASCULAR REACTIVITY

Ouabain is an endogenous substance occurring in the plasma in the nano molar range, that has been proposed to increase vascular resistance an d induce hypertension. This substance acts on the alpha-subunit of Na,K+-ATPase inhibiting the Na+-pump activity. In the vascular smooth mu scle this effect leads to intracellular Na+ accumulation that reduces the activity of the Na+/Ca2+ exchanger and to an increased vascular to ne. It was also suggested that circulating ouabain, even in the nanomo lar range, sensitizes the vascular smooth muscle to vasopressor substa nces. We tested the latter hypothesis by studying the effects of ouaba in in the micromolar and nanomolar range on phenylephrine (PE)-evoked presser responses. The experiments were performed in normotensive and hypertensive rats in vivo, under anesthesia, and in perfused rat tail vascular beds. The results showed that ouabain pretreatment increased the vasopressor responses to PE in vitro and in vivo. This sensitizati on after ouabain treatment was also observed in hypertensive animals w hich presented an enhanced vasopressor response to PE in comparison to normotensive animals. It is suggested that ouabain at nanomolar conce ntrations can sensitize vascular smooth muscle to vasopressor stimuli possibly contributing to increased tone in hypertension.