Key result
Adrenal Sry gene delivery raises systolic blood pressure ~30 mmHg vs vector controls in rats.
Why the study?
A locus on the SHR Y chromosome, potentially the Sry gene, was shown to increase blood pressure in SHR and SHR/y rats, but its direct effect on adrenal medullary function and blood pressure in normotensive rats was unclear.
Does exogenous Sry delivery to the adrenal medulla increase blood pressure and catecholamines in normotensive WKY rats?
Does exogenous Sry delivery to the adrenal medulla increase blood pressure and catecholamines in normotensive WKY rats?
Mean Difference: 30
Absolute Event Rate: 160% vs 130%
p-value: p=<0.05
Exogenous Sry delivery to the adrenal medulla increases blood pressure and sympathetic nervous system activity in normotensive rats, supporting Sry as a candidate gene for hypertension.
No immediate clinical implications; leaves open Sry's role in human hypertension pending further validation.
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.
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Ely et al. (2007) studied Normotension (n=24). Sry gene delivery (Sry1/pcDNA3.1(-)) vs. Empty vector control (pcDNA3.1(-)) was evaluated on Systolic blood pressure at 2-3 weeks (MD 30, p=<0.05). Delivery of the Sry gene to the adrenal medulla of normotensive WKY rats increased systolic blood pressure by 30 mmHg compared to vector controls.
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