Indapamide-induced prevention of myocardial fibrosis in spontaneous hypertension rats is not nitric oxide-related.
We studied the effect of thiazide-like diuretic--indapamide on fibrosis development in the left ventricle of young spontaneously hypertensive rats (SHR) and assessed the involvement of nitric oxide in this process. Six-week-old male SHR were treated with indapamide (1 mg/kg/day) for six weeks. Age-matched SHR were used as hypertensive and Wistar-Kyoto rats (WKY) as normotensive control. Systolic blood pressure was measured by tail-cuff plethysmography. Nitric oxide synthase (NOS) activity, protein expressions of endothelial (eNOS) and inducible NOS (iNOS), myocardial fibrosis and collagen type I and III were determined in the left ventricle. Indapamide treatment partially prevented SBP increase in SHR (SHR+Indapamide: 157+/-4, SHR: 171+/-3, WKY: 119+/-3 mmHg). Indapamide prevented myocardial fibrosis development in SHR, but without affecting collagen type I to type III ratio. Indapamide did not affect NOS activity as well as eNOS and iNOS protein expressions in the left ventricles evaluated by both Western blot and immunohistochemically. In conclusion, our results indicate that indapamide-induced prevention of myocardial fibrosis is not mediated by nitric oxide-related mechanism.
Janega
P
P
Department of Pathology, Faculty of Medicine, Comenius University, Bratislava, Slovak Republic. pavol.janega@fmed.uniba.sk
Kojsová
S
S
Jendeková
L
L
Babál
P
P
Pechánová
O
O
D000818:Animals; D001391:Azo Compounds; D001794:Blood Pressure / Q000502:physiology; D009202:Cardiomyopathies / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D024042:Collagen Type I / Q000378:metabolism; D024061:Collagen Type III / Q000378:metabolism; D004396:Coloring Agents; D004232:Diuretics / Q000627:therapeutic use*; D005355:Fibrosis; D005609:Free Radicals / Q000378:metabolism; D007190:Indapamide / Q000627:therapeutic use*; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D009569:Nitric Oxide / Q000502:physiology*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D016277:Ventricular Function, Left / Q000187:drug effects / Q000502:physiology; D020257:Ventricular Remodeling / Q000502:physiology
D001391:Azo Compounds; D024042:Collagen Type I; D024061:Collagen Type III; D004396:Coloring Agents; D004232:Diuretics; D005609:Free Radicals; C009798:C.I. direct red 80; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; D007190:Indapamide