Role of haematocrit in mediating the actions of chronic erythropoietin treatment on blood pressure and renal haemodynamics in the rat.
1. This investigation aimed to study the effect of chronic administration of human recombinant erythropoietin on haematocrit, blood pressure, renal cortical and papillary resistances and vascular responsiveness to vasoconstrictor agents. 2. Rats were treated with placebo or 25, 50 or 100 units/kg erythropoietin subcutaneously, every other day for 3 weeks. Animals were then anaesthetized with sodium pentobarbitone and were prepared for laser-Doppler flowmetry measurement in the renal cortex and papilla. 3. Haematocrit in the placebo-treated group was 48.0 +/- 0.5% and was raised to 52.5 +/- 0.7, 55.9 +/- 0.8 and 62.4 +/- 1.1% (all P < 0.05) by the chronic administration of 25, 50 and 100 units/kg doses of the hormone, respectively. Blood pressure was 107 +/- 1 mmHg in the placebo-treated group and was elevated to 116 +/- 2 and 130 +/- 1 mmHg (both P < 0.05), respectively, by the two highest doses of erythropoietin. Cortical and papillary perfusions were reduced at the highest dose of erythropoietin, but calculated resistances were increased by 15 and 40% (P < 0.05) at 50 and 100 units/kg doses of the hormone, respectively. 4. Infusion of the vasopressor hormones vasopressin and phenylephrine caused increases in blood pressure and decreases in renal cortical and papillary perfusion, the magnitudes of which were only marginally changed by the highest dose of the erythropoietin. Angiotensin II increased blood pressure and decreased cortical perfusion, and the magnitudes of these responses were unchanged by the chronic treatment with erythropoietin. 5. Acute graded increases in haematocrit resulted in significantly (P < 0.05) raised blood pressure above a value of 58%.(ABSTRACT TRUNCATED AT 250 WORDS)
Huang
C
C
Department of Physiology, Medical School, Birmingham, U.K.
Davis
G
G
Johns
E J
EJ
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004921:Erythropoietin / Q000494:pharmacology*; D006400:Hematocrit; D007668:Kidney / Q000098:blood supply / Q000187:drug effects*; D008297:Male; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects
D011994:Recombinant Proteins; D004921:Erythropoietin; D000804:Angiotensin II; D001127:Arginine Vasopressin; D010656:Phenylephrine