Role of erythropoietin and nitric oxide in modulating the tone of human renal interlobular and subcutaneous arteries from uraemic subjects.
This study investigated potential reasons why erythropoietin (EPO) given therapeutically to patients with renal failure may increase peripheral, but not renal, vascular resistance. This was done by comparing the effects of EPO on resting tension in normal renal interlobular and subcutaneous vessels from uraemic patients. In human subcutaneous arteries from uraemic subjects, noradrenaline- and KCl-induced vasoconstrictions were enhanced when nitric oxide (NO) production was blocked with N(G)-nitro-L-arginine methyl ester (L-NAME), but were unaffected by EPO, while acetylcholine- and bradykinin-induced concentration-dependent relaxations were markedly attenuated by L-NAME, but not by EPO. The noradrenaline- and KCl-induced vasoconstrictions of human renal interlobular arteries were unaffected by the presence of L-NAME, but were attenuated by EPO (20 units.ml(-1)) by some 33% (P<0.01); this effect was enhanced by the co-administration of L-NAME. Acetylcholine and bradykinin caused comparable dilatations of the interlobular arteries; the response to the former was attenuated by L-NAME, but none of these responses were changed by EPO. EPO given alone, at a concentration of either 0.1 or 20 units.ml(-1), had no effect on basal resting tone. NO production mediated both acetylcholine- and bradykinin-induced relaxation in this vessel type. In contrast, in the interlobular arteries there was no indication of NO modulating the level of vasoconstriction, and it only mediated acetylcholine-induced dilation. These acute responses to EPO only partially explain its differential effects on the vasculature in renal failure.
Wu
X C
XC
Department of Physiology, The Medical School, Birmingham B15 2TT, U.K.
Richards
N T
NT
Johns
E J
EJ
D000109:Acetylcholine / Q000494:pharmacology; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001158:Arteries / Q000187:drug effects; D001920:Bradykinin / Q000494:pharmacology; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004921:Erythropoietin / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009599:Nitroprusside / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D012077:Renal Artery / Q000187:drug effects*; D012867:Skin / Q000098:blood supply*; D014511:Uremia / Q000503:physiopathology*; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
D019332:Endothelin-1; D004791:Enzyme Inhibitors; D014665:Vasodilator Agents; D004921:Erythropoietin; D009599:Nitroprusside; D011189:Potassium Chloride; D019001:Nitric Oxide Synthase; D000109:Acetylcholine; D001920:Bradykinin; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine