title: Reduction of resistance artery stiffness by treatment with the AT(1)-receptor antagonist losartan in essential hypertension.
abstract: In spontaneously hypertensive rats resistance artery structure, endothelial dysfunction and geometry-independent wall stiffness were reduced by an angiotensin AT(1)-receptor antagonist. In previous studies of human hypertension, interruption of the renin-angiotensin system corrected small artery structure and endothelial dysfunction, whereas the beta-blocker atenolol did not. We hypothesized that the AT(1)R antagonist losartan, but not the beta-blocker atenolol, would reduce stiffness of gluteal subcutaneous small arteries in essential hypertensive patients. Seventeen untreated mild essential hypertensive patients (47+/-2 years; 75% male) were randomly assigned in double-blind fashion to losartan or atenolol treatment for one year. Small, resistance size arteries were studied on pressurized myographs. Blood pressure (mmHg) was reduced (p<0.01) from 145 +/- 4/101 +/- 2 and 147 +/- 6/98 +/- 2 to 128 +/- 4/86 +/- 2 and 131 +/- 3/84 +/- 1 by losartan and atenolol, respectively. The media/lumen ratio of small arteries was unaffected by atenolol (8.3+/-0.3% before and 8.8+/-0.5% after treatment). In contrast, losartan reduced media/lumen ratio from 8.4+/-0.4% to 6.7+/-0.3% (p<0.01). Whereas isobaric elastic modulus was unaffected by either treatment, geometry-independent stiffness (slope of elastic modulus vs. stress) was reduced from 9.7+/-1.2 to 6.1+/-0.9 (P<0.05) under losartan treatment, but was unchanged by atenolol (8.2+/-1.3 to 7.8+/-0.6). In conclusion, treatment with losartan reduced stiffness and structural alterations of subcutaneous resistance arteries of previously untreated essential hypertensive patients, whereas atenolol failed to do so.
authors.affiliation: Multidisciplinary Research Group on Hypertension, Clinical Research Institute of Montreal, Montreal, Quebec, H2W 1R7, Canada.
authors.forename: J B
authors.initials: JB
authors.lastname: Park
authors.forename: H D
authors.initials: HD
authors.lastname: Intengan
authors.forename: E L
authors.initials: EL
authors.lastname: Schiffrin
mesh_terms: D000328:Adult; D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001158:Arteries / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects; D002081:Buttocks; D004548:Elasticity; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology*; D019808:Losartan / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D044140:Receptor, Angiotensin, Type 1; D012867:Skin / Q000098:blood supply*; D014655:Vascular Resistance
chemical_list: D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D044140:Receptor, Angiotensin, Type 1; D019808:Losartan