Sry delivery to the adrenal medulla increases blood pressure and adrenal medullary tyrosine hydroxylase of normotensive WKY rats

BMC Cardiovasc Disord. 2007 Feb 26:7:6. doi: 10.1186/1471-2261-7-6.

Abstract

Background: Our laboratory has shown that a locus on the SHR Y chromosome increases blood pressure (BP) in the SHR rat and in WKY rats that had the SHR Y chromosome locus crossed into their genome (SHR/y rat). A potential candidate for this Y chromosome hypertension locus is Sry, a gene that encodes a transcription factor that is responsible for testes development and the Sry protein may affect other target genes.

Methods: The following study examined if exogenous Sry would elevate adrenal Th, adrenal catecholamines, plasma catecholamines and blood pressure. We delivered 10 mug of either the expression construct, Sry1/pcDNA 3.1, or control vector into the adrenal medulla of WKY rats by electroporation. Blood pressure was measured by the tail cuff technique and Th and catecholamines by HPLC with electrochemical detection.

Results: In the animals receiving Sry there were significant increases after 3 weeks in resting plasma NE (57%) and adrenal Th content (49%) compared to vector controls. BP was 30 mmHg higher in Sry injected animals (160 mmHg, p < .05) compared to vector controls (130 mmHg) after 2-3 weeks. Histological analysis showed that the electroporation procedure did not produce morphological damage.

Conclusion: These results provide continued support that Sry is a candidate gene for hypertension. Also, these results are consistent with a role for Sry in increasing BP by directly or indirectly activating sympathetic nervous system activity.

Publication types

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

MeSH terms

  • Adrenal Medulla / cytology
  • Adrenal Medulla / drug effects*
  • Adrenal Medulla / enzymology*
  • Animals
  • Blood Pressure / drug effects*
  • Electroporation
  • Gene Transfer Techniques
  • Male
  • Norepinephrine / blood
  • Rats
  • Rats, Inbred WKY
  • Sex-Determining Region Y Protein / administration & dosage*
  • Sex-Determining Region Y Protein / genetics
  • Sex-Determining Region Y Protein / pharmacology
  • Tyrosine 3-Monooxygenase / metabolism*

Substances

  • Sex-Determining Region Y Protein
  • Tyrosine 3-Monooxygenase
  • Norepinephrine