gms | German Medical Science

Objective: Investigations demonstrated a beneficial effect of EPO in traumatic brain injury, SAH, and stroke. The underlying mechanisms are not completely clarified so far. However, besides a neuroprotective effect an interfering with the activity of the NO-pathway or the attenuation of the potency of vasocontractile factors was postulated resulting in an improved CBF. Aim of the present study was, therefore, to characterize the effect of EPO on the potency of vasocontractile and vasodilating factors on the cerebrovasculature.

Methods: The basilar artery (BA) was removed from male rats, divided in ring segments and prepared for measurement of isometric force in an organ bath. Integrity of the endothelium and media was tested functionally. Concentration-effect curves (CECs) were constructed in absence or presence of EPO (100 IU/ml) by cumulative application. In segments under resting tension the contractile effect of endothelin-1 (ET-1) and 5-hydroxytryptamine (5-HT) was determined. After precontraction with PGF F2α the vasorelaxant potency of 8-Br-cGMP, sodium nitroprusside (SNP) and acetylcholine (ACh) were analyzed. Contraction is given in percent of 124 mM K+ force, vasodilation in percent of pre-contraction. CECs were compared by the maximum effect (E_max) and the pD₂.

Results: Both ET-1 and 5-HT induced a dose dependent contraction in presence (EPO+) and absence (EPO-) of EPO. For ET-1 (E_max: 73±3% (EPO+), vs. 75±5% (EPO-) and pD₂: 7.97±0.07 (EPO+) vs. 7.83±0.12 (EPO-)) CECs were not significantly different. Also for 5-HT non-significant changes in presence of EPO occurred (E_max: 62±4% (EPO+) vs. 78±4% (EPO-); pD₂: ‑7.00±0.075 (EPO+) vs. -6.88±0.14 (EPO-)). ACh, 8-Br-cGMP, and SNP induced dose-dependent relaxations. E_max of both ACh and SNP was not significantly changed in EPO+ and EPO-. In contrast, the sensitivity was significantly reduced in EPO+ for both compounds (ACh-pD₂: -6,44±0,10 (EPO+) vs. -6,91±0,13 (EPO-); SNP-pD₂: -4,62±0,15 (EPO+) vs. -5,23±0,21 (EPO-)). However, no significant changes of 8-Br-cGMP are effected by EPO (E_max: 76±2% (EPO+) vs. 80±8% (EPO-); pD₂: -3.75±0.03 (EPO+) vs. -3.65±0.04 (EPO-)).

Conclusions: The present data shows that EPO had no effect to the vasoconstriction by ET-1 and 5-HT in physiological rat BA. After EPO the NO donator SNP and ACh have a less sensitivity to the arteries. Therefore, our data may indicate that EPO interacts with sGC and eNOS and reduces the NO efficacy in the cerebrovasculature under physiological conditions.