Antihypertensive treatment and renal damage: amlodipine exerts protective effect through the polyol pathway.
Besides generating renal damage, hypertension plays an important role in the progression of diabetic nephropathy. The fructose-fed rat is a well-established model both of high blood pressure and renal impairment, which is similar to diabetic nephropathy. To clarify the relationship between hypertension, glucose metabolism, and kidney remodeling, we investigated the renal level of Glut 1 and Glut 5, their relation to fibrosis and the effects of an antihypertensive drug on renal damage. Twenty-four male WK rats were divided into three groups: 8 animals received a fructose-enriched diet, 8 a control diet, and 8 animals a high-fructose diet plus amlodipine (5 mg/Kg). After six weeks of treatment, we observed a significant increase in Glut 5, fibronectin, and sorbitol in fructose-fed rats compared with control and amlodipine-treated animals; there was a positive correlation between Glut 5 and fibronectin levels (r = 0.63). Glut 1 levels were similar in all three groups, whereas collagen IV was higher in fructose-fed rats; amlodipine prevented the increase of collagen IV and sorbitol. Collagen I was statistically higher in the fructose group than in the other two groups. Therefore, prolonged fructose feeding results in renal fibrosis via polyol pathway overactivity that can be prevented by means of an antihypertensive drug.
Bernobich
Elena
E
Department of Internal Medicine, University of Trieste, Cattinara Hospital, Italy. e.bernobich@fmc.units.it
Cosenzi
Alessandro
A
Campa
Cristiana
C
Zennaro
Cristina
C
Sasso
Franco
F
Paoletti
Sergio
S
Bellini
Giuseppe
G
D000284:Administration, Oral; D017311:Amlodipine / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000818:Animals; D001786:Blood Glucose; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D024042:Collagen Type I / Q000737:chemistry / Q000378:metabolism; D024141:Collagen Type IV / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D004032:Diet; D004195:Disease Models, Animal; D005353:Fibronectins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D005632:Fructose / Q000008:administration & dosage / Q000009:adverse effects; D051272:Glucose Transporter Type 1; D051296:Glucose Transporter Type 5; D006973:Hypertension / Q000139:chemically induced / Q000150:complications / Q000188:drug therapy*; D007150:Immunohistochemistry / Q000379:methods; D007328:Insulin / Q000097:blood; D007668:Kidney / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D007674:Kidney Diseases / Q000139:chemically induced / Q000150:complications / Q000188:drug therapy*; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000737:chemistry / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D011108:Polymers / Q000009:adverse effects / Q000378:metabolism*; D051381:Rats; D011921:Rats, Inbred WKY; D013012:Sorbitol / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism
D001786:Blood Glucose; D024042:Collagen Type I; D024141:Collagen Type IV; D005353:Fibronectins; D051272:Glucose Transporter Type 1; D051296:Glucose Transporter Type 5; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D011108:Polymers; C495679:Slc2a1 protein, rat; C024617:polyol; D017311:Amlodipine; D005632:Fructose; D013012:Sorbitol