FACTORS INVOLVED IN THE EFFECTS OF LOSARTAN ON ENDOTHELIAL DYSFUNCTION INDUCED BY AGING IN SHR

In the present study we investigated the effects of losartan (10 mg/kg /day; 12 weeks) on acetylcholine (Ach) induced relaxations in isolated mesenteric vascular beds (MVB) from adult and elderly spontaneous hyp ertensive rats (SHR). Experiments were done in absence or presence of either the NO synthesis inhibibitor, L-NAME (10(-5) mol/liter), L-NAME + indomethacin (10(-5) mol/liter) or L-NAME + indomethacin + KCI (10( -5) mol/liter), to evaluate the participation of the factors (NO, PGs and EDHF, respectively) mediating Ach-relaxations. Systolic blood pres sure levels were comparable in both groups. However, urinary nitrites excretion and Ach-response was lower in elderly than in adult SHR. The presence of L-NAME and L-NAME + indomethacin only reduced Ach-relaxat ions in untreated elderly SHR. Further addition of KCl to the perfusio n media totally blunted Ach-relaxation in both groups. The calculated participation of endothelium-derived hyperpolarizing factor (EDHF) in Ach-relaxations was higher than that of nitric oxide (NO) and prostagl andins in both groups, although the EDHF component was lower in elderl y when compared to adult SHR. Losartan treatment reduced blood pressur e levels and enhanced dose-related Ach-relaxations and urinary nitrite s in both groups. Presence of L-NAME and L-NAME + indomethacin blunted the enhancements induced by losartan on Ach-relaxations in both adult and elderly SHR. Further addition of KCl to the perfusion media total ly blunted Ach-relaxation in both groups. The calculated participation of NO in Ach-relaxations was increased by losartan in both groups. Ne ither EDHF or prostanoids (PGs) components were clearly affected by lo sartan. In conclusion, (1) diminished EDHF availability accounts for t he reduced Ach-relaxations produced by aging in MVB from SHR; (2) the enhancement of Ach-relaxations produced by losartan seems to be depend ent on an increased NO availability; and (3) angiotensin LI via angiot ensin I type 1 receptor (AT(1)) plays an important role in the deleter ious consequences of aging on endothelial function in SHR.