CHRONIC-RENAL-FAILURE AND HUMAN GROWTH-HORMONE TREATMENT DO NOT MODIFY ENDOTHELIUM-DEPENDENT REACTIONS IN THE RAT AORTA IN-VITRO

1 Growth hormone (GH) increases glomerular filtration rate and renal p lasma flow and decreases renal vascular resistance. Sustained GH-induc ed hyperfiltration might be undesirable in children with chronic renal failure (CRF) who are receiving recombinant human GH (rhGH) therapy. 2 In order to determine the effect of CRF on vascular reactivity and t he modifications induced by rhGH administration, two endothelium-depen dent effects, acetylcholine relaxation and decrease of contractile res ponse to noradrenaline, were studied in aorta segments of various grou ps of male Sprague-Dawley rats: CRF rats (CRF, n = 8) with serum urea nitrogen (SUN) 68+/-16 mg dl(-1) (mean+/-SEM), CRF rats treated with i ntraperitoneal rhGH at 10 IU kg(-1) day(-1) for 13 days (CRFGH, n = 6, SUN = 88+/-15 mg dl(-1), sham operated rats (SHAM, n = 8, SUN: 21+/-1 mg dl(-1)) and control rats (CONTROL, n = 8, SUN 20+/-1 mg dl(-1), ho used in identical conditions but without undergoing surgical intervent ion or manipulation. CRF was induced by 5/6 two stage nephrectomy. 3 R ats were sacrificed and a segment of thoracic aorta was immediately re moved, cut into spirals, and suspended in organ baths according to sta ndard procedures. First, dose-response curves to noradrenaline and ace tylcholine relaxation, in strips previously exposed to noradrenaline, were determined. Then, the endothelium was removed and both dose-respo nse curves were repeated. Acetylcholine induced a greater relaxation, P < 0.05, in the aorta of CONTROL rats (82.6+/-6.1%) as compared with SHAM (60.3+/-4.7 %), CRF (60.0+/-6.8 %) and CRFGH (54.8+/-8.2 %) rats. 4 Endothelium removal only caused a greater contractile response to n oradrenaline (10(-9) and 3 x 10(-9) M) in the CONTROL group, P < 0.05. 5 No differences to acetylcholine and noradrenaline responses were fo und among the SHAM, CRF and CRFGH groups. 6 These results suggest that the endothelium-dependent vascular reactivity was modified by the exp erimental protocol to induce chronic renal failure but no further chan ges resulted from uraemia and rhGH treatment.