title: Salt-induced cardiac hypertrophy and interstitial fibrosis are due to a blood pressure-independent mechanism in Wistar rats.
abstract: High salt intake is a known cardiovascular risk factor and is associated with cardiac alterations. To better understand this effect, male Wistar rats were fed a normal (NSD: 1.3% NaCl), high 4 (HSD4: 4%), or high 8 (HSD8: 8%) salt diet from weaning until 18 wk of age. The HSD8 group was subdivided into HSD8, HSD8+HZ (15 mg . kg(-1) . d(-1) hydralazine in the drinking water), and HSD8+LOS (20 mg . kg(-1) . d(-1) losartan in the drinking water) groups. The cardiomyocyte diameter was greater in the HSD4 and HSD8 groups than in the HSD8+LOS and NSD groups. Interstitial fibrosis was greater in the HSD4 and HSD8 groups than in the HSD8+HZ and NSD groups. Hydralazine prevented high blood pressure (BP) and fibrosis, but not cardiomyocyte hypertrophy. Losartan prevented high BP and cardiomyocyte hypertrophy, but not fibrosis. Angiotensin II type 1 receptor (AT(1)) protein expression in both ventricles was greater in the HSD8 group than in the NSD group. Losartan, but not hydralazine, prevented this effect. Compared with the NSD group, the binding of an AT(1) conformation-specific antibody that recognizes the activated form of the receptor was lower in both ventricles in all other groups. Losartan further lowered the binding of the anti-AT(1) antibody in both ventricles compared with all other experimental groups. Angiotensin II was greater in both ventricles in all groups compared with the NSD group. Myocardial structural alterations in response to HSD are independent of the effect on BP. Salt-induced cardiomyocyte hypertrophy and interstitial fibrosis possibly are due to different mechanisms. Evidence from the present study suggests that salt-induced AT(1) receptor internalization is probably due to angiotensin II binding.
authors: Laboratory of Experimental Hypertension, University of São Paulo, São Paulo 01246-903, Brazil.
authors: Daniele N
authors: DN
authors: Ferreira
authors: Isis A
authors: IA
authors: Katayama
authors: Ivone B
authors: IB
authors: Oliveira
authors: Kaleizu T
authors: KT
authors: Rosa
authors: Luzia N S
authors: LN
authors: Furukawa
authors: Michella S
authors: MS
authors: Coelho
authors: Dulce E
authors: DE
authors: Casarini
authors: Joel C
authors: JC
authors: Heimann
mesh_terms: D000450:Aldosterone / Q000097:blood; D000804:Angiotensin II / Q000032:analysis; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage; D001794:Blood Pressure / Q000502:physiology*; D006332:Cardiomegaly / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology*; D024042:Collagen Type I / Q000032:analysis; D024061:Collagen Type III / Q000032:analysis; D004195:Disease Models, Animal; D004326:Drinking; D004435:Eating; D004452:Echocardiography; D005355:Fibrosis; D015870:Gene Expression; D006352:Heart Ventricles / Q000737:chemistry / Q000473:pathology; D006830:Hydralazine / Q000008:administration & dosage; D006973:Hypertension / Q000503:physiopathology / Q000517:prevention & control; D019808:Losartan / Q000008:administration & dosage; D008297:Male; D009206:Myocardium / Q000473:pathology*; D011188:Potassium / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1 / Q000032:analysis / Q000235:genetics / Q000502:physiology; D044139:Receptor, Angiotensin, Type 2 / Q000032:analysis; D012083:Renin / Q000097:blood; D012084:Renin-Angiotensin System / Q000235:genetics / Q000502:physiology; D012964:Sodium / Q000097:blood / Q000652:urine; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage*; D016212:Transforming Growth Factor beta / Q000032:analysis; D014556:Urine
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D024042:Collagen Type I; D024061:Collagen Type III; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D017673:Sodium Chloride, Dietary; D016212:Transforming Growth Factor beta; D000804:Angiotensin II; D006830:Hydralazine; D000450:Aldosterone; D012964:Sodium; D012083:Renin; D019808:Losartan; D011188:Potassium