Article
Effects of Erythropoietin on Retinal Capillary Flow in Humans
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Published: | August 10, 2005 |
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Background: Erythropoietin (EPO) affects the vascular tone by various pathogenetic mechanisms leading to elevated blood pressure in some subjects. We examined the effect of EPO on retinal capillary flow (RCF) taken as a mirror for cerebral capillary perfusion.
Methods: In an open clinical trial with blind endpoint evaluation 33 subjects (age, 29 ± 5 years) with normal (n=17; 24 hour blood pressure 121 ± 5/72 ± 5 mmHg) or mildly elevated 24 hour blood pressure(n=16; 136 ± 7/76 ± 8 mmHg) were enrolled. Scanning Laser Doppler Flowmetry was used to measure RCF before and after intrvenous (i.v.) administration of EPO (50 U/kg), and on the next day before and after infusions of NG-monomethyl-L-arginine (L-NMMA; 3 mg/kg) and L-arginine (100 mg/kg). After two weeks the protocol was repeated with the same dose of EPO being administered subcutanously (s.c.).
Results: After administration of i.v. EPO, RCF decreased from 344 ± 70 to 322 ± 49 arbitrary units (AU) (p< 0.05) in hypertensive but not in normotensive subjects (335 ± 81 vs. 336 ± 71 AU, p= n.s.). This effect on RCF in hypertensive subjects was not found with EPO being administered s.c. (RCF; 339 ± 37 vs 342 ± 50 AU, p= n.s.). On the second day after s.c., but not after i.v. administration of EPO, systolic ambulatory blood pressure correlated with the response of RCF to L-NMMA (r= - 0.42,
p= 0.02) and to L-arginine (r= 0.36, p=0.04). Similar values were found in the hypertensive subgroup (r= - 0.55, p= 0.04 after L-NMMA and r= 0.59, p= 0.03 after L-arginine).
Conclusions: I.v. EPO caused an immediate reduction in RCF and thereby potentially in cerebral capillary flow in hypertensive subjects. No such effect was observed after s.c. administration of EPO. There was an improvement of both basal and stimulated nitric oxide activity in the retinal capillary bed after s.c. but not after i.v. EPO. This points to a counterregulatory increase of NO activity. Thus, our data suggest that EPO should preferentially be administered s.c. in patients with arterial hypertension. Furthermore, s.c. (but not i.v.) EPO seems to increase retinal endothelial function at least in mild to moderate hypertensive subjects.
Sponsored by grants from the Deutsche Forschungsgemeinschaft (GK 750) and Hoffmann-La Roche AG, Grenzach-Wyhlen, Germany.