Combined treatment with the angiotensin-converting enzyme (ACE) inhibitor delapril and the diuretic indapamide prevented vascular damage in vital organs of salt-loaded stroke-prone spontaneously hypertensive rats (SHRsp). Whether the changes occurring after long-term hypertension could also be modulated in large arteries was investigated. Two-month-old SHRsp were salt loaded and treated with the drug regimen until they reached 50 +/- 10 mortality or around midlife. In a first experiment, delapril (12 mg/kg) and indapamide (1 mg/kg) were administered daily separately or in combination. In the second dose-finding experiment, delapril (6, 3, 1.5 mg/kg) and indapamide (0.5, 0.25, 0.125 mg/kg) in decreasing dose combinations were analyzed. Ultrastructural, histomorphometric, and biochemical studies were performed on the thoracic aorta. When compared with delapril (12 mg/kg) or indapamide (1 mg/kg) administered individually for 5 months, the combination 12 + 1 mg/kg was able to prevent the increase in extracellular matrix deposition observed in other treatment groups, as assessed by histomorphometry or 4-OH-proline biochemical determination. In the second experiment, a half-dose (delapril 6 mg/kg + indapamide 0.5 mg/kg) combination was similarly effective in counteracting fibrosis, but the other doses progressively failed. In the first experiment, the combination had a stabilizing effect on hypertension and stimulated diuresis. In the second experiment, arterial blood pressure values and sodium balance were not consistently affected by the treatments that antagonized fibrosis (i.e., delapril 6 mg/kg + indapamide 0.5 mg/kg and, less efficiently, delapril 3 mg/kg + indapamide 0.25 mg/kg). These results suggest that indapamide interacts with ACE inhibitors to limit aortic fibrosis independent of any well-established mechanism.
|Data di pubblicazione:||2002|
|Titolo:||Dose-Dependent Prevention of Fibrosis in Aorta of Salt-Loaded Stroke-Prone Spontaneously Hypertensive Rats by Combined Delapril and Indapamide treatment.|
|Autore/i:||Contri, Miranda; Taparelli, Francesca; M., Miselli; G., Pedrazzi; B., Bacchelli; Biagini, Giuseppe|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1097/01.FJC.0000019005.47976.45|
|Codice identificativo ISI:||WOS:000177704100008|
|Codice identificativo Scopus:||2-s2.0-0036708258|
|Codice identificativo Pubmed:||12198325|
|Citazione:||Dose-Dependent Prevention of Fibrosis in Aorta of Salt-Loaded Stroke-Prone Spontaneously Hypertensive Rats by Combined Delapril and Indapamide treatment / Contri, Miranda; Taparelli, Francesca; M., Miselli; G., Pedrazzi; B., Bacchelli; Biagini, Giuseppe. - In: JOURNAL OF CARDIOVASCULAR PHARMACOLOGY. - ISSN 0160-2446. - STAMPA. - 40(2002), pp. 388-398.|
|Tipologia||Articolo su rivista|
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