The Sry3 Y chromosome locus elevates blood pressure and renin-angiotensin system indexes

Gend Med. 2011 Apr;8(2):126-38. doi: 10.1016/j.genm.2010.11.014.

Abstract

Background: Sex-determining region Y (Sry) is a transcription factor. Our research group has shown that there are multiple copies of Sry in Wistar-Kyoto (WKY) and spontaneous hypertensive (SHR) rats, and that they have novel functions separate from testes determination.

Objective: We hypothesized that exogenously delivered Sry3 to the normotensive WKY male kidney would activate the renin-angiotensin system (RAS) and raise blood pressure (BP), based on previous in vitro studies.

Methods: Sry3 or control vector was electroporated to the left kidney of male WKY rats and the following measurements were taken: BP by telemetry, renin-angiotensin measures by radioimmunoassay, plasma and tissue catecholamines by HPLC with electrochemical detection, sodium by flame photometry, and inulin by ELISA.

Results: Sry3 increased BP 10 to 20 mm Hg compared with controls (P < 0.01) and produced a significant 40% decrease in urine sodium compared with controls (P < 0.05). Sry3 increased renal angiotensin II and plasma renin activity by >100% compared with controls (P < 0.01 and P < 0.05, respectively).

Conclusion: The findings presented here confirm and extend the argument for Sry3 as one of the genes responsible for the SHR hypertensive Y chromosome phenotype and are consistent with increased tissue RAS activity due to Sry3 and increased sodium reabsorption.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Blood Pressure / genetics*
  • Blood Pressure / physiology
  • Catecholamines / metabolism
  • Chromatography, High Pressure Liquid
  • Creatinine / metabolism
  • Electrophoresis
  • Enzyme-Linked Immunosorbent Assay
  • Genetic Markers
  • Glomerular Filtration Rate
  • Health Status Indicators
  • Hypertension / genetics*
  • Kidney / metabolism*
  • Male
  • Rats
  • Rats, Inbred WKY
  • Renin-Angiotensin System / genetics*
  • Renin-Angiotensin System / physiology
  • Risk Factors
  • Sex-Determining Region Y Protein / genetics
  • Sex-Determining Region Y Protein / metabolism
  • Y Chromosome / genetics*
  • Y Chromosome / metabolism

Substances

  • Catecholamines
  • Genetic Markers
  • Sex-Determining Region Y Protein
  • Creatinine