title: The effect of angiotensin II receptor blockade on insulin sensitivity and sympathetic nervous system activity in primary hypertension.
abstract: 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.
authors.affiliation: Department of Internal Medicine, Ullevaal University Hospital, Oslo, Norway.
authors.forename: A
authors.initials: A
authors.lastname: Moan
authors.forename: T
authors.initials: T
authors.lastname: Risanger
authors.forename: I
authors.initials: I
authors.lastname: Eide
authors.forename: S E
authors.initials: SE
authors.lastname: Kjeldsen
mesh_terms: D000328:Adult; D000368:Aged; D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds / Q000494:pharmacology*; D001786:Blood Glucose / Q000032:analysis; D001794:Blood Pressure / Q000187:drug effects; D005260:Female; D006801:Humans; D006973:Hypertension / Q000503:physiopathology*; D007093:Imidazoles / Q000494:pharmacology*; D007333:Insulin Resistance; D019808:Losartan; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000097:blood; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000503:physiopathology; D013777:Tetrazoles / Q000494:pharmacology*
chemical_list: D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D001786:Blood Glucose; D007093:Imidazoles; D013777:Tetrazoles; D019808:Losartan; D009638:Norepinephrine