O237	Telmisartan improves endothelial function and insulin sensitivity in non-obese patients with essential hypertension.
R.A.Benndorf, D.Appel, R.Maas, E.Schwedhelm, E.Silberhorn, R.H.Böger
Institute of Experimental and Clinical Pharmacology, University Hospital Hamburg-Eppendorf, Hamburg, DE.

Background: Endothelial dysfunction as characterized by reduced flow-mediated vasodilation (FMD) has prognostic value for future cardiovascular events. Hypertension and further cardiovascular pathologies associated with the highly prevalent metabolic syndrome, e. g. Hyperinsulinemia, are associated with endothelial dysfunction. Recent data indicate that AT1 receptor antagonists, e. g. telmisartan, may improve EDF in hypertensive subjects. Furthermore, telmisartan was reported to activate PPAR-γ receptors in vitro, thereby suggesting beneficial effects of telmisartan on insulin sensitivity in vivo. Methods: To investigate the effect of anti-hypertensive drugs on FMD and insulin sensitivity, 37 patients with essential hypertension (mean BMI 24.9) were randomized to receive telmisartan (n=12), the calcium channel blocker nisoldipine (n=13) or their combination (n=12) for 6 weeks in a prospective, parallel group study. FMD and endothelium-independent dilation (EID) measured by high resolution ultrasound as well as fasting plasma glucose (FPG) and insulin (FPI) levels were evaluated before, 3 weeks (low dose) and 6 weeks (high dose) after initiation of treatment. Results: At baseline, blood pressure, FMD ((mean+/-SEM) 5.61+/-0.49%), EID, FPG (5.3+/-0.02 mmol/l) and FPI levels (10.0+/-1.1 µU/l) were similar in all treatment groups. 24 h blood pressure was reduced after 6 weeks of treatment with telmisartan (-6.7 mm Hg; P<0.05), nisoldipine (-3.7 mm Hg; P ns), and their combination (-8.7 mm Hg; P<0.05). Telmisartan (10.91+/-1.36%; P<0.05) and the combination (11.55+/-1.50%; P<0.05) but not nisoldipine (5.93+/-1.08%; P ns) increased FMD, while the EID remained unchanged in all groups. Furthermore, we observed a reduction in FPI levels in the telmisartan group (-46.1+/-9.0%; P<0.05) and as a trend in the combination group (-27.6+/-15.6%; P ns) but not in the nisoldipine group (-6.4+/-18.0%; P ns), while FPG levels were not affected. We conclude from these data that telmisartan improves FMD and insulin sensitivity in patients with essential hypertension. Future studies will demonstrate whether these telmisartan-induced effects may contribute to a blood pressure-independent reduction in cardiovascular morbidity.

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