Delivery of sry1, but not sry2, to the kidney increases blood pressure and sns indices in normotensive wky rats

Abstract

BackgroundOur laboratory has shown that a locus on the SHR Y chromosome increases blood pressure (BP) in the SHR rat and in WKY rats with the SHR Y chromosome (SHR/y rat). A candidate for this Y chromosome hypertension locus is Sry, a gene that encodes a transcription factor responsible for testes determination. The SHR Y chromosome has six divergent Sry loci. The following study examined if exogenous Sry1 or Sry2 delivered to the kidney would elevate renal tyrosine hydroxylase, renal catecholamines, plasma catecholamines and telemetered BP over a 28 day period. We delivered 50 μg of either the expression construct Sry1/pcDNA 3.1, Sry2/pcDNA 3.1, or control vector into the medulla of the left kidney of normotensive WKY rats by electroporation. Weekly air stress was performed to determine BP responsiveness. Separate groups of animals were tested for renal function and plasma hormone patterns and pharmacological intervention using alpha adrenergic receptor blockade. Pre-surgery baseline and weekly blood samples were taken from Sry1 electroporated and control vector males for plasma renin, aldosterone, and corticosterone. BP was measured by telemetry and tyrosine hydroxylase and catecholamines by HPLC with electrochemical detection.ResultsIn the animals receiving the Sry1 plasmid there were significant increases after 21 days in resting plasma norepinephrine (NE, 27%) and renal tyrosine hydroxylase content (41%, p < .05) compared to controls. BP was higher in animals electroporated with Sry1 (143 mmHg, p < .05) compared to controls (125 mmHg) between 2–4 weeks. Also the pressor response to air stress was significantly elevated in males electroporated with Sry1 (41 mmHg) compared to controls (28 mmHg, p < .001). Sry2 did not elevate BP or SNS indices and further tests were not done. The hormone profiles for plasma renin, aldosterone, and corticosterone between electroporated Sry1 and control vector males showed no significant differences over the 28 day period. Alpha adrenergic receptor blockade prevented the air stress pressor response in both strains. Urinary dopamine significantly increased after 7 days post Sry electroporation.ConclusionThese results are consistent with a role for Sry1 in increasing BP by directly or indirectly activating renal sympathetic nervous system activity.

Review of the Y chromosome, Sry and hypertension

“…In addition to these molecular, neural and behavioral effects, we have delivered Sry to kidney and adrenal gland and increased BP and other phenotypes [24,25]. These differences would not be expected if Sry were non-functional in adult males.…”

“…Either Sry1/pcDNA3.1(−), Sry2, Sry3 or control pcDNA3.1(−) vector without Sry sequences were electroporated into the left kidney medulla or adrenal medulla of adult male WKY rats under anesthetic [24,25]. Sry transcripts from the the plasmid, cannot be distinguished from endogenous Sry, therefore the use of females for verification.…”

Genetic Polymorphism of Human Y Chromosome and Risk Factors for Cardiovascular Diseases: A Study in WOBASZ Cohort

“…Genetic variants of Y chromosome have been shown to predispose to hypertension in a series of rodent experiments [1]–[3] with a recent suggestion of direct involvement of variation in the SRY locus [4], [5]. In humans, it has been found that a hypertensive father, but not a hypertensive mother, determines blood pressure in male offspring [6].…”

Whole rat DNA array survey for candidate genes related to hypertension in kidneys from three spontaneously hypertensive rat substrains at two stages of age and with hypotensive induction caused by hydralazine hydrochloride

“…The relationship between kidney function and blood pressure is known to be influenced by numerous intrinsic and extrinsic factors, such as the renin-angiotensin system and catecholamine and aldosterone hormones (16,17). Previously, Sty1 (18), Edg1, Vcam1 (19), C1q, CD24 (20), SPON1 (21), Gstm1 (22), ACE-2 (23), AMPK, APLP2 (24), Ephx2, Ela1 (25) and Egln1 (26) were shown to be hypertension-related genes in SHR or SHRSP kidneys using a DNA microarray. In contrast to the reports, this study is the first attempt to compare gene expression profiles in the kidneys of three SHR substrains, SHR, SHRSP and M-SHRSP, employing WKY rats as controls and using DNA microarrays to survey for genes related to hypertension in these SHR substrains.…”