The influence of erythropoietin on the vascular responses of rat resistance arteries.
This study examined the effect of erythropoietin (EPO) on resting tension and on the responses of rat mesenteric and renal arcuate arteries in vitro to 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 half-maximal response (pEC50) were altered in the presence of 0.1 or 20 U ml-1 EPO. The thromboxane A2 receptor agonist U46619 induced a constriction 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 unchanged by NG-nitro-L-arginine methyl ester (10-4 m). Serotonin (10-9-10-5 M) caused a concentration-related vasoconstriction in renal arcuate arteries 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 induced 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 nitroprusside-induced relaxations were unaffected by EPO. The acetylcholine-mediated relaxations in renal arcuate arteries were unchanged by EPO. Bradykinin-induced relaxations in mesenteric and renal arcuate arteries were unaffected 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 unlikely to be due to acute interactions with agonist-mediated responses.
Wu
X C
XC
Department of Physiology, The Medical School, Birmingham B15 2TT, UK.
Richards
N T
NT
Johns
E J
EJ
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004921:Erythropoietin / Q000494:pharmacology*; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000502:physiology; D009994:Osmolar Concentration; D051381:Rats; D017208:Rats, Wistar; D012077:Renal Artery / Q000187:drug effects* / Q000502:physiology; D014655:Vascular Resistance; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology; D014666:Vasomotor System / Q000187:drug effects*
D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D004921:Erythropoietin