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TRANSLATIONAL PHYSIOLOGY

Elevated blood pressure and cardiac hypertrophy after ablation of the gly96/IEX-1 gene

Departments of ¹Internal Medicine, ²Physiology and Biomedical Engineering, ³Laboratory Medicine and Pathology, ⁴Pediatrics and Adolescent Medicine, ⁵Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Mayo Clinic Rochester, Rochester, Minnesota

Submitted 16 March 2005 ; accepted in final form 9 September 2005

ABSTRACT

gly96/IEX 1 is a growth- and apoptosis-regulating, immediate early gene that is widely expressed in epithelial and vascular tissues. In vascular tissues, expression of the gene is induced by mechanical stretch, and overexpression of the gene prevents injury-induced vascular smooth muscle hypertrophy and neointimal hyperplasia. We now show that deletion of the gly96/IEX-1 gene in mice is associated with development of elevated blood pressure, cardiac hypertrophy, and diminished fractional shortening of the left ventricle. Systolic blood pressure in conscious male gly96/IEX-1^–/– mice is 20–25 mmHg higher than in gly96/IEX-1^+/+ mice. Serum and/or urine concentrations of sodium, potassium, creatinine, angiotensin II, corticosterone, aldosterone, epinephrine, norepinephrine, prostaglandin E₂, thromboxane B₂, prostaglandin-6-keto-1, nitrites and nitrates, cAMP, and cGMP are normal in gly96/IEX-1^–/– mice. Alterations in dietary sodium intake do not alter blood pressure in gly96/IEX-1^–/– mice. Aortic mRNAs for endothelial nitric oxide synthase, guanylate cyclase-, and cGMP kinase-1 are increased in gly96/IEX-1^–/– mice. Treatment with N-nitro-L-arginine methyl ester or L-arginine does not alter blood pressure in gly96/IEX-1^–/– mice. Gly96/IEX-1^–/– mice respond to infused sodium nitroprusside with decrements in blood pressure similar to those seen in wild-type littermate mice. In contrast to gly96/IEX-1 transgenic mice that have abnormalities in immune function, gly96/IEX-1^–/– mice have normal lymphoid tissue architecture and a normal complement of T and B cells in lymphoid tissues. Ablation of the gly96/IEX-1 gene results in hypertension and cardiac hypertrophy, suggesting a novel role for this gene in cardiovascular physiology.

elevated blood pressure; apoptosis; lymphoid cells

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