The influence of erythropoietin on the vascular responses of rat resistance arteries

This study examined the effect of erythropoietin (EPO) on resting tension a nd on the responses of rat mesenteric and renal arcuate arteries in vitro t o a number of agonists as a possible cause of its blood pressure elevating properties when used therapeutically. Noradrenaline and potassium chloride induced concentration-dependent vasoconstrictions in both vessel types but the basal tension, maximum tension, and the -log concentration producing ha lf-maximal response (pEC(50)) were altered in the presence of 0.1 or 20 U m l(-1) EPO. The thromboxane A(2) receptor agonist U46619 induced a constrict ion of the renal arcuate arteries which was enhanced by EPO at 20 U ml(-1), from 1.68 +/- 0.34 to 2.64 +/- 0.39 mN mm(-1) (P < 0.01), but which was un changed by N-G-nitro-L-arginine methyl ester(10(-4) M) Serotonin (10(-9)-10 (-5) M) caused a concentration-related vasoconstriction in renal arcuate ar teries which was shifted to the right in the time control study (P < 0.001) but this was abolished by both 0.1 and 20 U ml(-1) of EPO. Acetylcholine i nduced a relaxation of precontracted mesenteric arteries by 95.4 +/- 1.64 % with an EC50 of 7.08 +/- 0.08 M which was reduced (P < 0.001) by 20 U ml(- 1) EPO to 81.7 +/- 3.56 % and 6.10 +/- 0.11 M, respectively. The sodium nit roprusside-induced relaxations were unaffected by EPO. The acetylcholine-me diated relaxations in renal arcuate arteries were unchanged by EPO. Bradyki nin-induced relaxations in mesenteric and renal arcuate arteries were unaff ected by both EPO concentrations. Together these data showed that EPO over a large concentration range had only minor effects on basal tension and the vascular responsiveness of both mesenteric and renal arcuate arteries. The mechanism whereby EPO causes a chronic elevation in blood pressure is unli kely to be due to acute interactions with agonist-mediated responses.