PMID: 16529550Mar 15, 2006Paper

A new antihypertensive agent that antagonizes the prohypertensive effect of endogenous ouabain and adducin

Cardiovascular & Hematological Agents in Medicinal Chemistry
Paolo ManuntaP Ferrari

Abstract

Endogenous Ouabain (EO) and Adducin enhance the Na-K pump function and play an important role in sodium homeostasis and blood pressure (BP) regulation. In the general population, plasma EO modulates BP either by inhibiting the prohypertensive effect of an excessive salt intake or counteracting the depressor action of normal-moderate salt intake. Almost 50% of hypertensive patients have increased circulating plasma levels of EO. EO has been associated both to left ventricular dysfunction and hypertrophy. A new antihypertensive agent, PST2238, (17beta-(3-furyl)-5beta-androstan-3beta, 14beta, 17alpha-triol a digitoxigenin derivative) able to selectively antagonize both the EO and adducin prohypertensive and molecular effects, has been developed. In hypertensive rats (MHS strain) carrying both adducin mutations and increased plasma EO and in ouabain-infused rats (OS), PST2238 lowers BP by normalizing the renal Na-K pump function. In OS rats, PST antagonized the cardiac and renal pro-hypertrophic ouabain effect associated to the activation of the Src-EGFr-ERK(1/2) signaling cascade. Phase 1 clinical studies demonstrated a high tolerability of PST2238. In a preliminary phase 2 study on 42 mild never-treated hypertensive patients, PST...Continue Reading

Citations

Jul 25, 2009·Journal of Comparative Physiology. B, Biochemical, Systemic, and Environmental Physiology·Yurong ZhangYanping Ren
Feb 7, 2009·Proceedings of the National Academy of Sciences of the United States of America·T L RadzyukevichJ A Heiny
Feb 6, 2010·Clinical and Experimental Pharmacology & Physiology·Yu-Rong Zhang, Zu-Yi Yuan
Nov 8, 2011·American Journal of Physiology. Heart and Circulatory Physiology·Mordecai P BlausteinW Gil Wier
Mar 17, 2010·Biochimica Et Biophysica Acta·Paolo ManuntaJohn M Hamlyn
Oct 19, 2010·Cellular and Molecular Life Sciences : CMLS·Marina R AmaidenCésar H Casale

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antihypertensive Agents: Mechanisms of Action

Antihypertensive drugs are used to treat hypertension (high blood pressure) which aims to prevent the complications of high blood pressure, such as stroke and myocardial infarction. Discover the latest research on antihypertensive drugs and their mechanism of action here.

Cardiomyopathy

Cardiomyopathy is a disease of the heart muscle, that can lead to muscular or electrical dysfunction of the heart. It is often an irreversible disease that is associated with a poor prognosis. There are different causes and classifications of cardiomyopathies. Here are the latest discoveries pertaining to this disease.