Angiotensin II-dependent increased expression of Na+-glucose cotransporter in hypertension.
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). Vmax 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 Km. 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, Vmax 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.
D000804:Angiotensin II / Q000378:metabolism*; D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001794:Blood Pressure; D002462:Cell Membrane / Q000201:enzymology; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D005947:Glucose / Q000493:pharmacokinetics; D006977:Hypertension, Renal / Q000378:metabolism* / Q000503:physiopathology*; D015151:Immunoblotting; D007672:Kidney Cortex / Q000378:metabolism; D019808:Losartan / Q000494:pharmacology; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D017257:Ramipril / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D051297:Sodium-Glucose Transporter 2
D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D009004:Monosaccharide Transport Proteins; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; C490300:Slc5a2 protein, rat; D051297:Sodium-Glucose Transporter 2; D000804:Angiotensin II; D012964:Sodium; D005947:Glucose; D019808:Losartan; D017257:Ramipril