Reduction of resistance artery stiffness by treatment with the AT(1)-receptor antagonist losartan in essential hypertension.

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.