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Improvement of endothelial function in diabetes mellitus: AT1 receptor antagonism vs. beta receptor blockade
Verbesserung der endothelialen Funktion bei Diabetes mellitus: AT1-Rezeptorantagonismus versus Betarezeptor-Blockade
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Veröffentlicht: | 11. November 2004 |
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Gliederung
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Endothelial dysfunction (ED) is an initial step in vascular disease and often present in diabetes mellitus. We wanted to determine the effects of angiotensin type-1 receptor antagonists (AT1A) and beta blockers (BB) on ED in diabetic rats.
Experiments were performed in streptozotocin (STZ)-induced diabetic Sprague Dawley (SD) rats treated with the AT1A candesartan (Can) (1mg/kg/d), or the BB metoprolol (Met) (30mg/kg/d) or vehicle and in age matched controls (n=9/group). Vasoactive responses were studied in in situ autoperfused hindquarters. The endothelial-dependent vasodilation was analyzed by induction of shear stress (S) by injection of Krebs-Henseleit solution (200µl/kg) and the non-endothelial-dependent dilation by application of sodium nitroprusside (SNP, 40µg/kg). Immunohistochemically intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 were quantified in relation to net quadriceps muscle area.
The vasodilatory endothelial-dependent and non-endothelial-dependent responses of SD-STZ were impaired compared to controls (S: amplitude (mmHg): 22.9±1.9 vs. 51.2±3; Integral (mmHg*s): 1093±83 vs. 2450±312; SNP: Integral (mmHg*s): 3638±671 vs. 6602±953; p<0.05). This was accompanied with an increased expression of ICAM-1 and VCAM-1 (Area fraction: 0.61±0.14 vs. 0.09±0.01 and 0.52±0.1 vs. 0.06±0.01; p<0.05). The endothelial-dependent response of SD-STZ-Can but not of SD-STZ-Met was improved compared to SD-STZ (Can: S: Amplitude: 38.9±3.1 vs. 22.9±1.9; Integral: 1844±160 vs. 1093±83; p<0.05; Met: S: Amplitude: 23.7±2.2 vs. 22.9±1.9; Integral: 1430±157 vs. 1093±83; n.s.). Neither Can nor Met improved the non-endothelial-dependent response. Can suppressed the expression of VCAM-1 (0.07±0.01 vs. 0.52±0.1; p<0.05) but not of ICAM-1. Met had no effect on immunoreactivity.
Treatment with Can but not with Met shows vascular-protective effects in diabetic ED. As VCAM-1 expression is decreased, Can may elicit anti-inflammatory mechanisms.