Why the study?
Does PST 2238 reduce blood pressure and organ hypertrophy in hypertension associated with increased endogenous ouabain?
Does PST 2238 reduce blood pressure and organ hypertrophy in hypertension associated with increased endogenous ouabain?
PST 2238 is a promising selective agent for treating hypertension associated with elevated endogenous ouabain levels by antagonizing its effects on blood pressure and organ hypertrophy.
May warrant investigation in ouabain-related hypertension; leaves open clinical translation from in vivo data alone.
Elevated levels of the endogenous ouabain (EO), a closely related isomer of ouabain, are implicated in rat and human hypertension and in related cardiovascular complications. The pathogenetic mechanisms through which EO affects the cardiovascular system involve the modulation of the renal Na/K-ATPase, implicated in renal tubular sodium reabsorption, and the activation of signal transduction pathways, promoting the transcription of growth-related genes. Experimental and clinical evidence on rats and humans stimulated the pharmacological research for developing novel anti-hypertensive agents able to antagonize the cellular and molecular alterations mediated by EO. Among them, the digitoxigenin derivate, PST 2238, has been selected for its ability to antagonize the ouabain-induced effects on blood pressure and organ hypertrophy at oral doses of microgram/kg/day in vivo. The pharmacological selectivity and safety of PST 2238 suggests that the compound may be effective for the treatment of those forms of hypertension in which renal sodium handling alterations and cardiovascular complications are associated with increased production of EO.
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Ferrandi Mara (2005) studied this question.
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