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.

• Klíčová slova
• captopril, fibrosis, hypertension, lactacystin, melatonin, remodelling,
• MeSH
• acetylcystein škodlivé účinky   analogy a deriváty   MeSH
• antihypertenziva aplikace a dávkování   farmakologie   MeSH
• fibróza MeSH
• hypertenze chemicky indukované   farmakoterapie   etiologie   MeSH
• kaptopril aplikace a dávkování   farmakologie   MeSH
• krysa rodu Rattus MeSH
• melatonin aplikace a dávkování   farmakologie   MeSH
• modely nemocí na zvířatech MeSH
• NG-nitroargininmethylester škodlivé účinky   MeSH
• potkani Wistar MeSH
• remodelace komor účinky léků   MeSH
• srdeční komory účinky léků   patologie   MeSH
• světlo škodlivé účinky   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH
• Názvy látek
• acetylcystein MeSH
• antihypertenziva MeSH
• kaptopril MeSH
• lactacystin MeSH Prohlížeč
• melatonin MeSH
• NG-nitroargininmethylester MeSH

Exposure of rats to continuous light attenuates melatonin production and results in hypertension development. This study investigated whether hypertension induced by continuous light (24 hours/day) exposure induces heart and aorta remodelling and if these alterations are prevented by melatonin or angiotensin converting enzyme inhibitor captopril. Four groups of 3-month-old male Wistar rats (10 per group) were treated as follows for six weeks: untreated controls, exposed to continuous light, light-exposed, and treated with either captopril (100 mg/kg/day) or melatonin (10 mg/kg/day). Exposure to continuous light led to hypertension, left ventricular (LV) hypertrophy and fibrosis, and enhancement of the oxidative load in the LV and aorta. Increase in systolic blood pressure by continuous light exposure was prevented completely by captopril and partially by melatonin. Both captopril and melatonin reduced the wall thickness and cross-sectional area of the aorta and reduced the level of oxidative stress. However, only captopril reduced LV hypertrophy development and only melatonin reduced LV hydroxyproline concentration in insoluble and total collagen in rats exposed to continuous light. In conclusion, captopril prevented LV hypertrophy development in the continuous light-induced hypertension model, while only melatonin significantly reduced fibrosis. This antifibrotic action of melatonin may be protective in hypertensive heart disease.

• MeSH
• antihypertenziva terapeutické užití   MeSH
• hypertenze farmakoterapie   MeSH
• inhibitory ACE terapeutické užití   MeSH
• kaptopril terapeutické užití   MeSH
• krevní tlak účinky léků   MeSH
• krysa rodu Rattus MeSH
• melatonin terapeutické užití   MeSH
• oxidační stres účinky léků   MeSH
• potkani Wistar MeSH
• světlo * MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antihypertenziva MeSH
• inhibitory ACE MeSH
• kaptopril MeSH
• melatonin MeSH