2010
DOI: 10.1126/scitranslmed.3001815
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Adducin- and Ouabain-Related Gene Variants Predict the Antihypertensive Activity of Rostafuroxin, Part 1: Experimental Studies

Abstract: Essential hypertension is a complex, multifactorial disease associated with a high cardiovascular risk and whose genetic-molecular basis is heterogeneous and largely unknown. Although multiple antihypertensive therapies are available, the large individual variability in drug response results in only a modest reduction of the cardiovascular risk and unsatisfactory control of blood pressure in the hypertensive population as a whole. Two mechanisms, among others, are associated with essential hypertension and rel… Show more

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Cited by 40 publications
(42 citation statements)
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“…Conversely, the NB congenic substrain showed SBP levels similar to those of MNS rats (Table 1) (Tripodi et al, 2004;Ferrandi et al, 2010b). The prolonged oral treatment with rostafuroxin (100 mg/kg per day for 8 weeks, starting from weaning) reduced SBP in MHS and NA rats, but was inactive in MNS rats (Table 1), confirming previous data (Ferrandi et al, 2010a). HR was significantly lower in MHS as compared with MNS rats, and rostafuroxin treatment did not affect HR in any rat strain (Table 1).…”
Section: Rat Modelssupporting
confidence: 79%
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“…Conversely, the NB congenic substrain showed SBP levels similar to those of MNS rats (Table 1) (Tripodi et al, 2004;Ferrandi et al, 2010b). The prolonged oral treatment with rostafuroxin (100 mg/kg per day for 8 weeks, starting from weaning) reduced SBP in MHS and NA rats, but was inactive in MNS rats (Table 1), confirming previous data (Ferrandi et al, 2010a). HR was significantly lower in MHS as compared with MNS rats, and rostafuroxin treatment did not affect HR in any rat strain (Table 1).…”
Section: Rat Modelssupporting
confidence: 79%
“…It relies on its ability to inhibit the interaction of mutant a-adducin-or ouabain-activated Na,K-ATPase at the Src-SH2 domain, preventing Src activation and the Srcdependent Na,K-ATPase phosphorylation and activation at the renal tubular level (Ferrandi et al, 2010a). The result is the disruption of the complex signaling cascade downstream to Src-Na,K-ATPase induced by rostafuroxin, which is associated with the normalization of BP in hypertensive rats and patients (Ferrandi et al, 2010a;Lanzani et al, 2010).…”
Section: Discussionmentioning
confidence: 99%
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“…Furthermore, an antihypertensive drug, rostafuroxin, exerts its antihypertensive and also antihypertrophic effects by antagonizing the Src-dependent signaling triggered by ouabain (46). In vivo, rostafuroxin acts as an antagonist of endogenous ouabain and has been shown to disrupt an interaction between Src kinase and adducin (47,48). Thus, ouabain may affect the adducin and Src interaction.…”
Section: Possible Mechanisms Of Nak-atpase-mediated Cell Signaling?mentioning
confidence: 99%