Kidney Week

Abstract: FR-PO365

Lanosterol Synthase and Endogenous Ouabain Cooperate in Blood Pressure Control

Session Information

• Hypertension and CVD: Clinical, Outcomes, Trials
  October 26, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Hypertension and CVD

• 1402 Hypertension and CVD: Clinical, Outcomes, and Trials

Authors

• Lanzani, Chiara, IRCCS San Raffaele Scientific Institute, Milan, Italy

Chiara Lanzani,

• Fontana, Simone, IRCCS San Raffaele Scientific Institute, Milan, Italy

Simone Fontana,

• Simonini, Marco, IRCCS San Raffaele Scientific Institute, Milan, Italy

Marco Simonini,

• Brioni, Elena, IRCCS San Raffaele Scientific Institute, Milan, Italy

Elena Brioni,

• Messaggio, Elisabetta, IRCCS San Raffaele Scientific Institute, Milan, Italy

Elisabetta Messaggio,

• Cuka, Ermira, IRCCS San Raffaele Scientific Institute, Milan, Italy

Ermira Cuka,

• Delli carpini, Simona, IRCCS San Raffaele Scientific Institute, Milan, Italy

Simona Delli carpini,

• Citterio, Lorena, IRCCS San Raffaele Scientific Institute, Milan, Italy

Lorena Citterio,

• Zagato, Laura, IRCCS San Raffaele Scientific Institute, Milan, Italy

Laura Zagato,

• Hamlyn, John, University of Maryland, Baltimore, Baltimore, Maryland, United States

John Hamlyn,

• Manunta, Paolo, IRCCS San Raffaele Scientific Institute, Milan, Italy

Paolo Manunta,

Background

Endogenous Ouabain (EO) is stress hormone secreted from the adrenal glands in response to hemodynamic stimuli. Long term body sodium has been shown to modulate plasma EO levels according to Lanosterol synthase gene polymorphisms. The present study explores the effect of acute saline load according to LSS Gene variants and circulating EO levels in a large cohort of naïve hypertensive patients (NHPs).

Methods

Basal EO was measured in 713 NHPs for acute saline test phenotypes. For the analysis, patients were divided in groups according to tertile distributions of basal EO : 1^st group EO <167 pmol/L; 2^nd group EO >167 pmol/L and < 268 pmol/L; 3^rd group EO >268 pmol/L. In the three groups, we evaluated 1) changes in EO, 2) interaction with LSS variants and 2) blood pressure effects.

Results

Circulating EO was higher among Salt Sensitive NHPs, (geometric mean 224.04 vs 199.81 pM/L,p =0.005) no significant modification was observed during acute maneuvers. However, a significant modulation (p=0.044) was observed between elevated circulating EO and the LSS A variant, and the DBP rise after saline infusion.

Conclusion

These results confirm the role of EO in salt sensitive hypertension. Patients carrying at least one LSS A variant in the presence of elevated EO show an modulatory effect on diastolic BP. The higher affinity of the LSS A variant at tissue levels may account for the enhanced vascular response in these patients. The present findings support a role for LSS and EO in salt adaptation.