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

ABSTRACT: Our 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 mug 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.In 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.These results are consistent with a role for Sry1 in increasing BP by directly or indirectly activating renal sympathetic nervous system activity.

SUBMITTER: Ely D

PROVIDER: S-EPMC2699329 | biostudies-literature | 2009 Jun

REPOSITORIES: biostudies-literature

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

Ely Daniel D Milsted Amy A Dunphy Gail G Boehme Shannon S Dunmire Jeff J Hart Mike M Toot Jonathon J Turner Monte M

BMC physiology 20090605

<h4>Background</h4>Our 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 c ...[more]

PMID: 19500370

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Project description:Background Trimethylamine oxide (TMAO) is a biomarker in cardiovascular and renal diseases. TMAO originates from the oxidation of trimethylamine (TMA), a product of gut microbiota and manufacturing industries-derived pollutant, by flavin monooxygenases (FMOs). The effect of chronic exposure to TMA on cardiovascular and renal systems is undetermined. Methods Metabolic, hemodynamic, echocardiographic, biochemical and histopathological evaluations were performed in 12-week-old male SPRD rats receiving water (controls) or TMA (200 or 500 µM/day) in water for 18 weeks. TMA and TMAO levels, the expression of FMOs and renin-angiotensin system (RAS) genes were evaluated in various tissues. Results In comparison to controls, rats receiving high dose of TMA had significantly increased arterial systolic blood pressure (126.3 ± 11.4 vs 151.2 ± 19.9 mmHg; P = 0.01), urine protein to creatinine ratio (1.6 (1.5; 2.8) vs 3.4 (3.3; 4.2); P = 0.01), urine KIM-1 levels (2338.3 ± 732.0 vs. 3519.0 ± 953.0 pg/mL; P = 0.01), and hypertrophy of the tunica media of arteries and arterioles (36.61 ± 0.15 vs 45.05 ± 2.90 µm, P = 0.001 and 18.44 ± 0.62 vs 23.79 ± 2.60 µm, P = 0.006; respectively). Mild degeneration of renal bodies with glomerulosclerosis was also observed. There was no significant difference between the three groups in body weight, water-electrolyte balance, echocardiographic parameters and RAS expression. TMA groups had marginally increased 24 h TMA urine excretion, whereas serum levels and 24 h TMAO urine excretion were increased up to 24-fold, and significantly increased TMAO levels in the liver, kidneys and heart. TMA groups had lower FMOs expression in the kidneys. Conclusions Chronic exposure to TMA increases blood pressure and increases markers of kidney damage, including proteinuria and KIM-1. TMA is rapidly oxidized to TMAO in rats, which may limit the toxic effects of TMA on other organs. Supplementary Information The online version contains supplementary material available at 10.1186/s12967-022-03687-y.

Project description:Leandra dasytricha (A. Gray) Cong. is widely distributed in the south of Brazil and is commonly used for cardiovascular and kidney ailments. For this study, we used male Wistar normotensive rats (NTRs) and spontaneously hypertensive rats (SHRs) to verify the effects of the ethyl acetate fraction (EAF) obtained from L. dasytricha leaves on isolated aorta relaxation and in the arterial blood pressure. The EAF was analyzed by LC-DAD-MS, and several components were annotated, including hydrolysable tannins, triterpenes, and O- and C-glycosylated dihydrochalcones, such as the most intense ion peak relative to C-hexosyl phloretin (nothofagin; compound number 13). The EAF caused a concentration and endothelium-dependent relaxation of the aorta in both NTRs and SHRs. This effect was abolished in the endothelium-denuded aorta. L-NAME, a nonselective nitric oxide synthase inhibitor, and ODQ, a soluble guanylate cyclase inhibitor, entirely blocked the EAF-induced relaxation. The presence of a muscarinic receptor antagonist or a cyclooxygenase inhibitor did not alter the EAF's effectiveness in relaxing the aorta. The preincubation with tetraethylammonium, a Ca2+-activated K+ channel blocker, and with 4-aminopyridine, a voltage-dependent K+ channel blocker, significantly interfered with the EAF's relaxation. However, the incubation with glibenclamide, an ATP-sensitive K+ channel blocker, and barium chloride, an inward-rectifier K+ channel blocker, did not interfere with the EAF-induced relaxation. The EAF treatment also caused a dose-dependent decrease in the mean arterial pressure, systolic arterial pressure, and diastolic arterial pressure of both NTRs and SHRs, without significantly interfering with heart rate values. In conclusion, this study demonstrated the EAF-induced vasorelaxant and hypotensive actions, primarily dependent on the endothelium function and mainly with the participation of the nitric oxide and Ca2+-activated and voltage-dependent K+ channels.

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

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

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