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

The following study examined if exogenous Sry would elevate adrenal Th, adrenal catecholamines, plasma catecholamines and blood pressure. We delivered 10 μg 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.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.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.We have shown previously that there is a locus on the SHR Y chromosome that increases blood pressure (BP) about 20–25 mmHg [1,2]. Backcrosses of the SHR Y chromosome into WKY rats show a significant Y chromosome BP increase of 20 mmHg [3]. Further studies showed that the SHR Y chromosome increased several indices of SNS activity [4]. We demonstrated that renal norepinephrine (NE) turnover rate is higher by 100% [5] and renal NE content is 44% higher in males with the Y chromosome from an SHR [5]. Our recent studies indicate that a candidate gene for this SNS and BP effect is Sry, a transcription factor on the Y chromosome that is the testis determining factor [6]. Sry expression has been reported in testis, the brain and in additional tissues that have BP relevance in adult humans and rodents [7-9]. Recently, we demonstrated that Sry increased tyrosine hydroxylase (Th) promoter activity in transfected PC12 cells [6] although much of the effect was indirect. Th catal