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Angiotensin II-dependent increased expression of Na⁺-glucose cotransporter in hypertension

¹Department of Molecular Biomedicine, Centro de Investigación y Estudios Avanzados del Instituto Politécnico Nacional, Mexico City 07360; ²Department of Pharmacology, Facultad de Medicina, Universidad Autónoma de San Luis Potosi, San Luis Potosí 78000; and ³Department of Pathology, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City 14080, Mexico

Submitted 21 March 2003 ; accepted in final form 11 September 2003

Glucose uptake is increased in hypertension. Thus we investigated Na⁺-glucose cotransporter (SGLT2) activity and expression in proximal tubules from renovascular hypertensive rats. Sham-operated rats, aortic coarctation rats, and aortic coarctation rats treated with either ramipril (2.5 mg·kg^-1·day^-1 for 21 days) or losartan (10 mg·kg^-1·day^-1 for 21 days) were used. Na⁺-dependent glucose uptake was measured in brush-border membrane vesicles (BBMV). V_max in BBMV from hypertensive rats was greater compared with those from normotensive rats (3 ± 0.2 vs. 1.5 ± 0.1 nmol·mg protein^-1·min^-1) without a change in K_m. Renal immunostaining was greater, and Western blot analysis and RT-PCR showed a higher expression of SGLT2 in hypertensive rats than in normotensive rats (1,029 ± 71 vs. 5,003 ± 292, 199 ± 15 vs. 95 ± 10, and 1.4 ± 0.2 vs. 0.3 ± 0.1 arbitrary units, respectively). In rats treated with either ramipril or losartan, V_max decreased to 2.1 ± 0.3 and 1.8 ± 0.4 nmol·mg protein^-1·min^-1, respectively, as well as did the intensity of immunostaining and levels of protein and mRNA. We suggest that in renovascular hypertension, angiotensin II induced SGLT2 via the AT₁ receptor, which was evidenced at both the functional and expression levels, probably contributing to increased absorption of Na⁺ and thereby to the development or maintenance of hypertension.

renovascular hypertension; sodium reabsorption; ANG II type 1 receptor; glucose uptake

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