title: Chronic renal failure and human growth hormone treatment do not modify endothelium-dependent reactions in the rat aorta in vitro.
abstract: 1. Growth hormone (GH) increases glomerular filtration rate and renal plasma flow and decreases renal vascular resistance. Sustained GH-induced 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 the modifications induced by rhGH administration, two endothelium-dependent effects, acetylcholine relaxation and decrease of contractile response to noradrenaline, were studied in aorta segments of various groups 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 intraperitoneal 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), housed in identical conditions but without undergoing surgical intervention or manipulation. CRF was induced by 5/6 two stage nephrectomy. 3. Rats were sacrificed and a segment of thoracic aorta was immediately removed, cut into spirals, and suspended in organ baths according to standard procedures. First, dose-response curves to noradrenaline and acetylcholine relaxation, in strips previously exposed to noradrenaline, were determined. Then, the endothelium was removed and both dose-response 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 noradrenaline (10(-9) and 3 x 10(-9)M) in the CONTROL group, P < 0.05. 5. No differences to acetylcholine and noradrenaline responses were found among the SHAM, CRF and CRFGH groups. 6. These results suggest that the endothelium-dependent vascular reactivity was modified by the experimental protocol to induce chronic renal failure but no further changes resulted from uraemia and rhGH treatment.
authors.affiliation: Department of Medicine, School of Medicine, University of Oviedo, Spain.
authors.forename: M J
authors.initials: MJ
authors.lastname: Garcia de Boto
authors.forename: A
authors.initials: A
authors.lastname: Cobo
authors.forename: J
authors.initials: J
authors.lastname: Rodríguez
authors.forename: P
authors.initials: P
authors.lastname: Fernández
authors.forename: C
authors.initials: C
authors.lastname: Rey
authors.forename: F
authors.initials: F
authors.lastname: Santos
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000503:physiopathology; D002648:Child; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology*; D019382:Human Growth Hormone / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007676:Kidney Failure, Chronic / Q000503:physiopathology*; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
chemical_list: D019382:Human Growth Hormone; D000109:Acetylcholine; D009638:Norepinephrine