Abstract
In a previous study we demonstrated that blood plasma from an anephric rabbit and uremic patients contains solutes which are capable of depressing the sympathetic nerve-mediated smooth muscle contractions of guinea pigs in vitro. The degree of depression was greater in the blood plasma containing solutes with a molecular weight (MW) of less than 500 daltons.
Accordingly, in the first series of the present experiments, the effects of individual uremic toxins urea, uric acid, creatinine and methylguanidine (MG) on the nerve-mediated smooth muscle contractions were examined in vitro. When tested mt concentrations similar to those in blood plasma of patients with severe chronic renal failure (CRF). urea (200mg/dl), creatinine (20mg/dl) and MG (200μg/dl) produced no significant change in the amplitude of contraction, whereas uric acid (10mg/dl) produced a slight but significant increase of 7±5%(mean±S.D., n=7) as compared with the control, i.e., the amplitude of contraction before application of the substances.Simultaneous application of these four substances produced the same slight increase as did the application of uric acid alone.
In the second series, the effects of changing concentrations of some electrolytes in the normal bathing solution (Krebs solution) to those in blood plasma of patients with severe CRF were similarly examined on the contractions. The high K+ (9mM) solution produced a significant increase of 14±11%(n=7).On the other hand, the low Ca++ (1mM) aulution or high Mg++ (2mM) solution caused the contractions to be depressed by 56±25%(n=9) and 13±4%(n=6), respectively.Simultaneous changes in these three electrolyte concentrations in the Krebs solution produced an inhibition of 60±21%(n=8), and this solution containing the afore-mentioned four substances produced an inhibition of 53±24%(n=8), which was smaller by 7% because of the increasing effect of the four substances on the contractions.Thus, the present study indicates the possibility that the depression by the plasma solutes with a low MW observed in the previous study could be attributable to changes in the electrolyte, namely concentrations.However, further studies are obviously necessary to confirm this conclusion.Ca++, concentrations.However, further studies are obviously necessary to confirm this conclusion.
