Lactacystin is a proteasome inhibitor that interferes with several factors involved in heart remodelling. The aim of this study was to investigate whether the chronic administration of lactacystin induces hypertension and heart remodelling and whether these changes can be modified by captopril or melatonin. In addition, the lactacystin-model was compared with NG-nitro-l-arginine-methyl ester (L-NAME)- and continuous light-induced hypertension. Six groups of three-month-old male Wistar rats (11 per group) were treated for six weeks as follows: control (vehicle), L-NAME (40 mg/kg/day), continuous light (24 h/day), lactacystin (5 mg/kg/day) alone, and lactacystin with captopril (100 mg/kg/day), or melatonin (10 mg/kg/day). Lactacystin treatment increased systolic blood pressure (SBP) and induced fibrosis of the left ventricle (LV), as observed in L-NAME-hypertension and continuous light-hypertension. LV weight and the cross-sectional area of the aorta were increased only in L-NAME-induced hypertension. The level of oxidative load was preserved or reduced in all three models of hypertension. Nitric oxide synthase (NOS) activity in the LV and kidney was unchanged in the lactacystin group. Nuclear factor-kappa B (NF-κB) protein expression in the LV was increased in all treated groups in the cytoplasm, however, in neither group in the nucleus. Although melatonin had no effect on SBP, only this indolamine (but not captopril) reduced the concentration of insoluble and total collagen in the LV and stimulated the NO-pathway in the lactacystin group. We conclude that chronic administration of lactacystin represents a novel model of hypertension with collagenous rebuilding of the LV, convenient for testing antihypertensive drugs or agents exerting a cardiovascular benefit beyond blood pressure reduction.

• Keywords
• captopril, fibrosis, hypertension, lactacystin, melatonin, remodelling,
• MeSH
• Acetylcysteine adverse effects   analogs & derivatives   MeSH
• Antihypertensive Agents administration & dosage   pharmacology   MeSH
• Fibrosis MeSH
• Hypertension chemically induced   drug therapy   etiology   MeSH
• Captopril administration & dosage   pharmacology   MeSH
• Rats MeSH
• Melatonin administration & dosage   pharmacology   MeSH
• Disease Models, Animal MeSH
• NG-Nitroarginine Methyl Ester adverse effects   MeSH
• Rats, Wistar MeSH
• Ventricular Remodeling drug effects   MeSH
• Heart Ventricles drug effects   pathology   MeSH
• Light adverse effects   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Comparative Study MeSH
• Names of Substances
• Acetylcysteine MeSH
• Antihypertensive Agents MeSH
• Captopril MeSH
• lactacystin MeSH Browser
• Melatonin MeSH
• NG-Nitroarginine Methyl Ester MeSH