Effect of 1-week treatment with erythropoietin on the vascular endothelial function in anaesthetized rabbits.
Chronic administration of erythropoietin (EPO) is often associated with hypertension in animals and humans. The aim of this study was to estimate whether 1-week treatment with EPO can affect the vascular endothelial function. Rabbits were given with EPO (400 iu kg(-1) s.c.) or saline each other day for 1 week. Hypotensive responses to intravenously given acetylcholine (ACh), endothelium-independent nitric oxide donors (NOC7, nitroprusside and nitroglycerin) and prostaglandin I2 were tested before and after administration of N(G)-nitro-L-arginine methyl ester (L-NAME), a specific nitric oxide synthase inhibitor, under pentobarbitone anaesthesia. Blood haemoglobin concentration in EPO group was significantly higher than that in control group, whereas baseline values of aortic pressure, heart rate and femoral vascular resistance were similar. The dose of ACh (172 ng kg(-1)) requiring for a 15 mmHg hypotension from the baseline in EPO group was apparently higher than that (55 ng kg(-1)) in control group. On the contrary, hypotensive responses to NOC7, nitroprusside, nitroglycerin and prostaglandin I2 were comparable between two groups. The extent of ACh-induced hypotension did not correlate with haemoglobin concentration. L-NAME significantly inhibited the ACh-induced vasodilating response in control group but did not in EPO group. In another set of rabbits, the same treatment with EPO also decreased vasodilating responses to carbachol, bradykinin and substance P besides ACh as compared with control group. These results indicate that 1-week treatment with EPO selectively attenuates depressor responses to endothelium-dependent vasodilators in anaesthetized rabbits, most likely due to inhibition of endothelial nitric oxide synthase.
Noguchi
K
K
Department of Pharmacology, School of Medicine, Faculty of Medicine, University of the Ryukyus, Nishihara, Okinawa, Japan. noguchi@med.u-ryukyu
Yamashiro
S
S
Matsuzaki
T
T
Sakanashi
M
M
Nakasone
J
J
Miyagi
K
K
Sakanashi
M
M
D000109:Acetylcholine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000758:Anesthesia; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D011464:Epoprostenol / Q000494:pharmacology; D004921:Erythropoietin / Q000008:administration & dosage* / Q000494:pharmacology*; D005269:Femur / Q000098:blood supply / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006454:Hemoglobins / Q000032:analysis; D007022:Hypotension / Q000139:chemically induced; D066298:In Vitro Techniques; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D010424:Pentobarbital; D011817:Rabbits; D013997:Time Factors; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
D006454:Hemoglobins; D020030:Nitric Oxide Donors; D014665:Vasodilator Agents; D004921:Erythropoietin; D009569:Nitric Oxide; D011464:Epoprostenol; D019001:Nitric Oxide Synthase; D010424:Pentobarbital; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester