The effects of angiotensin II receptor antagonist losartan on elastic properties of aorta in patients with mild to moderate essential hypertension were assessed. The ascending aortic distensibility in 26 patients (48±3 years) with mild to moderate essential hypertension before and after 12 weeks of treatment with losartan (50 mg/day) was evaluated by using two-dimensional echocardiography. M-mode measurements of aortic systolic (D5) and diastolic diameter (Dd) were taken at a level approximately 3 cm above the aortic valve. Simultaneously, cuff brachial artery systolic (SBP) and diastolic (DBP) pressures were measured. Aortic pressure-strain elastic modulus (Ep) was calculated as Dd×(SBP−DBP)/(Ds−Dd)×1333 and stiffness index beta (β) was defined as Dd×Ln (SBP/DBP)/(Ds−Dd). Blood pressure significantly decreased from 148±13/95±9 mmHg to 138±12/88±8 mmHg (systolic blood pressure,P=0.001; diastolic blood pressure,P=0.003). There was no significant difference in pulse pressure before and after treatment with losartan (53±10 mmHg vs 50±7 mmHg). The distensibility of ascending aorta increased significantly as showed by the significant decrease in pressure-strain elastic modulus from 4.42±5.79×106 dynes/cm2 to 1.99 ±1.49×106 dynes/cm2 (P=0.02) and stiffness index beta from 27.4±32.9 to 13.3±9.9 (P=0.02). Although there was a weak correlation between the percent changes in pressure-strain elastic modulus and stiffness index beta and that in diastolic blood pressure after losartan treatment (r=0. 40,P=0.04 andr=0.55,P=0.004, respectively), no correlation was found between the percent changes in pressure-strain elastic modulus and stiffness index beta and that in systolic blood pressure (r=0.04,P=0.8 andr=0.24,P=0.2, respectively). Our study demonstrated that angiotensin II receptor antagonist losartan has a beneficial effect on aortic distensibility in patients with mild to moderate essential hypertension and this effect is partly independent of blood pressure reduction.
In this study antigen-independent factor in the pathogenesis of chronic rejection of organ transplants was examined. Kidney isografts and allografts were transplanted orthotopically into bilaterally nephroectomized rat recipients and studied functionally, morphologically and immunohistologically, at serial intervals up to 52 weeks after transplantation. Allograft recipients developed progressive proteinuria after 12 weeks, with gradual renal failure ultimately leading to death. At the same time, morphological changes, including progressive arteriosclerosis and glomerulosclerosis, tubular atrophy and interstitial fibrosis, developed. Immunohistologically, macrophages infiltrated glomeruli during this period and cytokines became unregulated. Our results showed that antigen-independent functional and morphological changes occurred in long-term kidney isografts and mimicked those appearing much earlier in allografts that reject chronically. Initial injury and extent of functioning renal mass is suggested to be important factor for such late changes.