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|Title:||Dual Effect of Nitrate Therapy for Cyclosporine-Induced Hypertension on Vascular and Platelet Morphofunctional Markers; An Animal Model||Authors:||Reis, F.
Lemos, E. Teixeira de
Garrido, A. P.
|Issue Date:||2007||Citation:||Transplantation Proceedings. 39:8 (2007) 2501-2506||Abstract:||The present study sought to evaluate the prevention and reversion effects of isosorbide-5-mononitrate (Is-5-Mn) on the development of hypertension (HT) and on the underlying vascular and platelet morphofunctional disturbances, using an animal model of cyclosporine (CsA)-induced HT. The following rat groups (n = 8) were tested: (1) a control group (orange juice, for 7 weeks); (2) the CsA group (5 mg/kg/d for 7 weeks); (3) the Is-5-Mn group (150 mg/kg/d, twice a day for 7 weeks); (4) the prevention group (Is-5-Mn + CsA) treated for 2 weeks with Is-5-Mn only and thereafter with both drugs for 7 weeks; (5) the curative group (CsA + Is-5-Mn) beginning 7 weeks after CsA and following thereafter with both drugs for 5 weeks. Blood pressure, lipid profile, vascular lesion, platelet aggregation and morphology, and platelet thromboxane A2/vascular prostacyclin equilibrium were evaluated. Is-5-Mn + CsA therapy prevented (systolic blood pressure [SBP]: 114.3 Â± 1.9 mm Hg, P < .001; diastolic blood pressure [DBP]: 97.0 Â± 3.3 mm Hg, P < .001) the CsA-induced HT (SBP: 146.2 Â± 4.5 mm Hg, P < .001; DBP: 124.9 Â± 4.5 mm Hg, P < .001 vs control: SBP: 111.6 Â± 0.7 mm Hg; DBP: 94.6 Â± 1.0 mm Hg), as well as the vascular lesion and the platelet morphofunctional disturbances. The curative group did not show attenuated CsA-induced BP increase; it showed further enhancement of the HT effect (SBP: 159.7 Â± 5.5 mm Hg, P < .05; DBP: 132.8 Â± 2.8 mm Hg), as well as worsened vascular lesions and platelet function, namely a disruption in the TXA2/PGI2 equilibrium. Our data suggested that Is-5-Mn therapy may be a valid choice to prevent the morphofunctional changes associated with CsA-induced HT, when used as a preventive therapy. A careful evaluation of the impact of nitrate therapy should be considered, particularly the negative effect on cardiovascular hemodynamics, when considering its use after previous CsA disturbances have been established.||URI:||http://hdl.handle.net/10316/4706||DOI:||10.1016/j.transproceed.2007.07.029||Rights:||openAccess|
|Appears in Collections:||FMUC Medicina - Artigos em Revistas Internacionais|
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