Effects of renin-angiotensin system inhibitors on density of rat myocardial, pericardial, and pulmonary mast cells in experimental heart failure

Abstract

The activation of the renin-angiotensin system (RAS) plays a critical role in the pathogenesis of car- diac failures (CFs). Using a model of experimental CFs, we studied the effects of lisinopril (LP) and fosinopril (FP) (inhibitors of the angiotensin-converting enzyme), as well as of losartan (LT, antagonist of angiotensin II receptors), on the density of multifunctional mast cells (MCs). RAS inhibitors were injected for 4 weeks begin- ning 4 weeks after two (with 24-h intervals) isoproterenol injections. MCs of different degrees of maturity were identified in paraffin sections stained with Alcian blue and Safranin. The CF severity was estimated based on functional echocardiogram parameters and on morphological criteria in histological sections. The MC density in the myocardiums of intact rats, as well as of rats with CFs that were and were not treated with drugs was relatively low, i.e., 3-4 cells/mm 2 . The MC density in pericardiums of intact rats was several times higher than in myocardiums, i.e., 35 ± 7 cells/mm 2 . In CFs, the density of pericardial MCs was 1.7 higher than in intact rats due to an increase in the density of immature cells stained with Alcian blue ( p < 0.05). Injections of LP increased the MC density 1.4-fold due to the density of mature cells stained with Safranin ( p < 0.01). Injections of FP and LT did not affect the MC density and the balance of cells of different degrees of maturity in the peri- cardium. In lungs, 96-99% of MCs were Alcian positive. In intact rats, rats with CF, and rats with CF treated with FP, the density of these cells was 30 cells/mm 2 . Injections of LP and LT decreased the density of pulmo- nary MCs to 7 cells/mm 2 ( p < 0.01) and 19 cells/mm 2 ( p < 0.05), respectively. The functional parameters of the heart were consistent with the data of the morphological analysis. The improvement of myocardial function was only noted in rats with CF treated with FP and LT. The obtained data show that, in the myocardiums, pericar- diums, and lungs of rats with CF, reaction of MCs (as the cell elements of the RAS tissue) to injections of inhib- itors of RAS was diverse. In the pericardium, injections of LP stimulated the maturation of resident MCs, as well as the replenishment of the population at the expense of immature cells that migrate from outside (by means of the migration of immature cells from the outside). This allows us to suggest us that the secretory activ- ity of these cells is intensified. Conversely, in lungs, injections of LP, like of LT, suppress the MC population.