Effect of 1-week treatment with erythropoietin on the vascular endothelial function in anaesthetized rabbits.

摘要: Chronic administration of erythropoietin (EPO) is often associated with hypertension in animals and humans. The aim this study was to estimate whether 1-week treatment EPO can affect the vascular endothelial function. Rabbits were given (400 iu kg−1 s.c.) or saline each other day for 1 week. Hypotensive responses intravenously acetylcholine (ACh), endothelium-independent nitric oxide donors (NOC7, nitroprusside nitroglycerin) prostaglandin I2 tested before after NG-nitro-L-arginine methyl ester (L-NAME), a specific synthase inhibitor, under pentobarbitone anaesthesia. Blood haemoglobin concentration group significantly higher than that control group, whereas baseline values aortic pressure, heart rate femoral resistance similar. dose ACh (172 ng kg−1) requiring 15 mmHg hypotension from apparently (55 ng kg−1) group. On contrary, hypotensive NOC7, nitroprusside, nitroglycerin comparable between two groups. extent ACh-induced did not correlate concentration. L-NAME inhibited vasodilating response but group. In another set rabbits, same also decreased carbachol, bradykinin substance P besides as compared group. These results indicate selectively attenuates depressor endothelium-dependent vasodilators anaesthetized most likely due inhibition synthase. Keywords: Erythropoietin, acetylcholine, haemoglobin, synthase, vasodilator Introduction Erythropoietin (EPO), which glycoprotein hormone secreted primarily kidney lowered blood O2 availability hypoxia, haemorrhage anaemia, acts on erythroid progenitor cells bone marrow, then increases peripheral supply by promoting their proliferation differentiation (Jelkmann, 1992). Medication has gained wide acceptance anaemia chronic renal failure. Development worsening generally considered serious adverse effect (Raine, 1988). Hypertension usually occurs within several weeks months onset accompanied increased haematocrit (Buckner et al., 1990). EPO-induced with, to, an increase resistance, been explained viscosity 1988; Schaefer 1988), loss hypoxia-induced vasodilation (Neff 1971). In addition, (Hb) circulation may theoretically augment trapping (NO), endogenous vasodilator (Martin & Moncada, However, these proposed explanations mechanism remain yet controversial. Recently, it shown receptors are found only endothelium (Anagnostou 1994; Yamaji 1996), reportedly causes acceleration migration 1990) angiogenesis (Carlini 1995b), endothelin-1 release vitro 1993; Bode Boger 1996). known play essential role regulating tone through generation potent vasoactive substances such NO and/or I2. Indeed, impaired suggested causative experimentally hypertensive rats (Hayakawa 1993) normotensive subjects familial history (Taddei Therefore, seems important examine responsiveness endothelium-derived NO. Thus, conducted repeated cause dysfunction. function vivo assessed comparing P, 3-(2-hydroxy-1-methylethyl-2-nitrosohydrazino)-N-methyl-1-propanamine (NOC7), sodium addition rabbits received its vehicle.