title: Effects of losartan on insulin sensitivity in severe hypertension: connections through sympathetic nervous system activity?
abstract: Angiotensin II (Ang II) is one of the most potent vasoconstrictors, and the first specific and orally available Ang II-receptor antagonist, losartan (MK-954, DuP-753), has now come into clinical use. The primary site of insulin resistance, as measured by the glucose clamp technique, is skeletal muscle. Losartan specifically blocks Ang II-induced vasoconstriction, namely causes vasodilation, and may thus increase glucose delivery to skeletal muscle. We used the euglycaemic hyper-insulinaemic glucose clamp technique to assess insulin sensitivity (glucose disposal rate, GDR) or insulin (I) sensitivity index (GDR/I). In 21-year-old men we found negative correlations between GDR/I and blood viscosity (r = -0.69), haematocrit (r = -0.65), fibrinogen (r = -0.50), cholesterol/HDL ratio (r = -0.45), triglycerides (r = -0.46), body mass index (r = -0.64), waist/hip ratio (r = -0.57), resting heart rate (r = -0.46) and diastolic blood pressure (DBP) (r = -0.43), and with DBP (r = -0.62) and plasma adrenaline (r = -0.36) during mental arithmetic stress. In the Losartan Severe Hypertension Study five patients with a record of DBP > or = 115 mm Hg were examined before and on losartan monotherapy for an average of 6 weeks. GDR increased 27% and plasma noradrenaline decreased 40% (P < 0.05 for both) during treatment with losartan. Calculated whole blood viscosity decreased on losartan (P = 0.04) and the changes in GDR correlated with the changes in viscosity (r = 0.89). These results suggest that losartan, possibly by a sympathicolytic effect, lowers blood viscosity, causes vasodilation, and improves insulin sensitivity in essential hypertension.
authors.affiliation: Department of Internal Medicine, Ullevaal University Hospital, Oslo, Norway.
authors.forename: A
authors.initials: A
authors.lastname: Moan
authors.forename: A
authors.initials: A
authors.lastname: Høieggen
authors.forename: G
authors.initials: G
authors.lastname: Nordby
authors.forename: I K
authors.initials: IK
authors.lastname: Eide
authors.forename: S E
authors.initials: SE
authors.lastname: Kjeldsen
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D000804:Angiotensin II / Q000037:antagonists & inhibitors*; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001713:Biphenyl Compounds / Q000008:administration & dosage / Q000627:therapeutic use*; D001786:Blood Glucose / Q000378:metabolism; D001809:Blood Viscosity / Q000187:drug effects; D015309:Glucose Clamp Technique; D006801:Humans; D006973:Hypertension / Q000097:blood* / Q000188:drug therapy* / Q000503:physiopathology; D007093:Imidazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D007333:Insulin Resistance / Q000502:physiology*; D019808:Losartan; D008297:Male; D013564:Sympathetic Nervous System / Q000187:drug effects; D013777:Tetrazoles / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D001786:Blood Glucose; D007093:Imidazoles; D013777:Tetrazoles; D000804:Angiotensin II; D019808:Losartan