The effect of angiotensin II receptor antagonism with losartan on glucose metabolism and insulin sensitivity.

OBJECTIVE: To investigate the metabolic effects of losartan (Cozaar) in patients with essential hypertension. METHODS: Twenty patients with mild hypertension (office blood pressure > 140/95 mmHg and home diastolic blood pressure > 90 mmHg) were examined in a double-blind, placebo-controlled cross-over study of 4 weeks of treatment with 50-100 mg losartan. The effects on glucose metabolism were assessed by euglycaemic glucose clamp examinations [glucose disposal rate (GDR, mg/kg per min)] and oral glucose-tolerance tests (OGTT). RESULTS: Supine blood pressure was reduced from 146 +/- 3/90 +/- 3 mmHg on placebo to 134 +/- 4/83 +/- 3 mmHg on losartan and the difference was maintained during 120 min of insulin infusion and glucose clamping. GDR was 6.2 +/- 0.5 mg/kg per min on placebo and 6.4 +/- 0.5 mg/kg per min on losartan. The glucose and insulin responses (the area under the curve) during OGTT were similar with placebo and losartan (0.86 +/- 0.3 versus 0.88 +/- 0.4 and 341 +/- 60 versus 356 +/- 60, respectively; arbitary units). Serum cholesterol was 5.3 +/- 0.2 mmol/l on placebo and 5.1 +/- 0.2 mmol/l losartan treatment. High-density lipoprotein cholesterol and triglycerides were, respectively, 1.1 +/- 0.1 and 1.5 +/- 0.2 mmol/l with placebo, and 1.1 +/- 0.1 and 1.4 +/- 0.1 mmol/l with losartan treatment. CONCLUSION: In mildly hypertensive patients, selective angiotensin II receptor antagonism with losartan for 4 weeks lowers blood pressure at rest and during 120 min of glucose clamping, and has neutral effects on insulin sensitivity, glucose metabolism and serum lipids.

The effect of angiotensin II receptor blockade on insulin sensitivity and sympathetic nervous system activity in primary hypertension.

The objective of this study was to investigate the effect of Losartan (NK-954, DuP-753), a new selective angiotensin II receptor antagonist, on insulin sensitivity and sympathetic nervous system activity in patients with severe primary hypertension. Five patients with a record of diastolic blood pressure (DBP) > or = 115 mmHg, currently either untreated or with DBP > 95 mmHg on antihypertensive treatment, were examined in an open study with the euglycemic glucose clamp examination before and after being treated with Losartan for an average of 6 weeks. The glucose disposal rate increased from 6.2 +/- 2.6 to 7.9 +/- 2.6 mg/kg x min (27%, p < 0.05) during treatment with Losartan. The insulin sensitivity index (glucose disposal rate divided by mean insulin concentration during clamp) increased from 7.7 +/- 4.5 to 10.1 +/- 4.1 arbitrary units (30%, p < 0.05). Plasma noradrenaline decreased from 1.87 +/- 0.53 to 1.11 +/- 0.13 nmol/l (40%, p < 0.05), while plasma adrenaline was unchanged (0.23 +/- 0.10 vs. 0.22 +/- 0.11 nmol/l, n.s.). Mean blood pressure decreased from 132 +/- 10 to 119 +/- 13 mmHg (p < 0.05) and heart rate was unchanged during treatment with Losartan. Thus, antihypertensive treatment with the new selective angiotensin II receptor antagonist Losartan seems to improve insulin sensitivity. A decrease in plasma noradrenaline on Losartan suggests a sympathicolytic effect which together with vasodilation may explain the fall in blood pressure and the improvement in insulin sensitivity.