No abstract

In CHF, the proportion of WBC and platelets that are ROS-positive is raised, possibly because cytosolic ROS-positive WBC and platelets are normally cleared in the lungs; this function is deficient in CHF while mitochondrial ROS production is increased. The raised numbers of circulating ROS-positive WBC and platelets amplify oxidative stress in CHF.

Abstract-Because nitric oxide (NO) inhibits aggregation and adhesion of blood platelets, NO may play a role in platelet-vessel wall interactions. Therefore, the purpose of this study was to investigate the involvement of endogenous NO in thromboembolic processes, as induced by wall puncture, in rabbit mesenteric arterioles and venules (diameters 20 to 43 m). In venules, inhibition of NO synthase by superfusion of the mesentery with N -nitro-L-arginine (L-NA; 0.1 mmol/L) significantly increased the duration of embolization (from 50 seconds to 511 seconds) and the number of emboli produced (from 2 to 11 emboli per vessel), while the median period of time needed to produce an embolus was not influenced. On the contrary, in arterioles, L-NA had no significant effect on embolization (duration of embolization: 426 seconds in the control and 382 seconds in the L-NA group, with 20 and 12 emboli per vessel, respectively). Addition to the L-NA superfusate of L-arginine (L-ARG; 1 mmol/L), the active precursor for endogenous NO synthesis, resulted in a complete reversal of the L-NA effects in venules, while addition of the inactive D-arginine (D-ARG; 1 mmol/L) had no effect. Addition of L-ARG and D-ARG had no significant effect in arterioles. Addition to the L-NA superfusate of the exogenous NO donor sodium nitroprusside (0.1 mol/L) also resulted in reversal of the L-NA effects in venules, while in arterioles, it slightly but significantly decreased embolization duration. The differences in effect of L-NA on embolization between arterioles and venules were not caused by differences in fluid dynamic conditions. It is concluded that the role of endogenous NO in inhibiting thromboembolic processes is more important in venules than in arterioles.

In the present study, we investigated renal microvascular responses to ANG-(1-7) and ANG IV. Diameter changes of small interlobular arteries, afferent arterioles, and efferent arterioles were assessed by using isolated perfused hydronephrotic rat kidneys. ANG-(1-7) and ANG IV concentration dependently decreased the diameters of all investigated renal microvessel, however, with a much lower potency than ANG II. The ANG II type 1 receptor blocker irbesartan completely reversed the responses to ANG-(1-7) and ANG IV, whereas the ANG II type 2 receptor blocker PD-123319 had no effect. Both ANG-(1-7) and ANG IV failed to alter renal microvascular constriction induced by ANG II. In addition, subnanomolar concentrations of ANG-(1-7) had no effect on the myogenic-induced tone of interlobular arteries and afferent arterioles. Thus our data indicate that at high concentrations, ANG-(1-7) and ANG IV are able to activate the ANG II type 1 receptor, thereby inducing renal microvascular constriction. The failure of ANG-(1-7) and ANG IV to reduce ANG II- and pressure-induced constrictions suggests that these fragments do not exert a vasodilator and/or ANG II antagonistic action in the kidney.

Platelet activation, as measured by the up-regulation of CD62p, is an early process, occurring not only within the dialyser, but across the entire length of the ECC. As CD62p remained unaltered after the administration of LMWH 10 min before the actual start of HD, this kind of activation is independent of LMWH. Considering PF4 however, a sharp increment was observed after the administration of LMWH and before the start of HD. This finding suggests that the PF4 release observed early in clinical HD is largely independent from the ECC, and is probably the result of LMWH-induced detachment from the endothelium. As the platelet serotonin content was relatively reduced and the plasma serotonin levels were elevated, platelets from chronic HD patients might be depleted due to chronic repetitive activation. Based on these data, it appears first, that PF4 is an inferior marker of platelet activation in clinical HD and second, that LMWH is a major contributor to HD-induced bio-incompatibility.