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Protective effects of nebivolol and reversal of endothelial dysfunction in diabetes associated with hypertension

Domenii publicaţii > Biologie + Tipuri publicaţii > Articol în revistã ştiinţificã

Autori: Adriana Georgescu , Doina Popov, Emanuel Dragan, Elena Dragomir , Elisabeta Badila

Editorial: Elsevier, European Journal of Pharmacology , 570, p.149-158, 2007.


This study aims to decipher the potential effects of nebivolol in prevention and/or regression of renal artery dysfunction in diabetes associated with hypertension. Renal arteries were isolated from 80 male mice divided into four experimental groups: (i) group D: diabetics, at 2months since streptozotocin injection; (ii) group Din: mice that at the initiation of streptozotocin diabetes were treated with 10mg/kg b.w./day nebivolol for 2 months, to test for the potential prevention of vascular dysfunction; (iii) group Dfin: mice that after 2months of diabetes were treated daily with 10mg/kg b.w./day nebivolol for additional 2 months, in order to follow the possible regression of the dysfunction, and (iv) controls (C), age-matched healthy animals. The following measurements were performed: arterial blood pressure, plasma glucose concentration, and the vascular
reactivity of the renal arteries in response to noradrenaline (10-4M), acetylcholine (10- 4M) and sodium nitroprusside (10-4M). To assess the
molecular mechanisms involved in the reactivity of the renal artery, the contribution of mitogen-activated protein kinase (MAP kinase) pathway
and of L-type voltage gated Ca2+ channels (in the contractile response to noradrenaline), of nitric oxide (NO) and Ca2+ activated K+ channels (in
the endothelium-dependent vasodilator response), and of cGMP (in the endothelium-independent vasodilator response) was examined by exposing
the arteries to corresponding inhibitors, and by using myograph and patch-clamp techniques, immunoblotting and NO assays. Results showed that,
group D was characterized by hyperglycemia (blood glucose concentration: 136.66 +/-177; 4.96mg/dl, a value ~ 65% increased compared to group C)and hypertension (systolic blood pressure: 145.66 +/-177; 5.96mm Hg, a value~ 34% increased compared to group C). Compared to group D, group Din was characterized by diminished blood glucose concentration (~ 1.6 fold), reduced systolic and diastolic blood pressure (~ 1.3 fold) and heart rate (~ 1.6 fold), as well as by increased contractile response of the renal artery to noradrenaline (~ 1.84 fold) and of the impeded vasodilator
response to acetylcholine (~ 1.81 fold) and sodium nitroprusside (~ 1.42 fold). Together, these effects demonstrate that administration of 10mg/kg
b.w./day nebivolol at the moment of diabetes induction has preventive effects, ameliorating diabetes dysfunctions. Compared to group D, group
Dfin was characterized by diminished glucose concentration (~ 1.3 fold), reduced systolic and diastolic blood pressure and heart rate (both ~ 1.2
fold), and by augmentation of contractile response of the renal artery to noradrenaline (~1.62 fold) and of vasodilator response to acetylcholine
(~ 1.13 fold) and sodium nitroprusside (~ 1.19 fold). These effects assess that administration of 10mg/kg b.w./day nebivolol after 2months of
diabetes contributes to regression of diabetes-associated dysfunctionalities. Nebivolol influenced the molecular mechanisms involved in renal artery
reactivity in diabetic and hypertensive mice: it increased the NO production and endothelial NO synthase (eNOS) protein expression, decreased
the expression of protein in L-type calcium channels and Ca2+ activated K+ channels, and diminished the MAP kinase activity. The reported data suggest that nebivolol may offer additional vascular protection for treating diabetes associated with hypertension.

Cuvinte cheie: artera renala, nebivolol, vasodilatare, disfunctia endoteliala, diabet, hipertensiune // Renal artery, Nebivolol, Vasodilation; Endothelial dysfunction, Diabetes, Hypertension