Aim: Rats with adenine-induced chronic renal failure (A-CRF) develop a reduced rate of relaxation of the thoracic aorta. The aim of this study was to elucidate the mechanisms underlying this abnormality.
Methods: Male Sprague Dawley rats received either chow containing adenine or were pair-fed with normal chow (controls). After 8-14 weeks, arterial function was analysed ex vivo using wire myography and the expression of proteins involved in vascular smooth muscle excitation-contraction coupling in the thoracic aorta was analysed.
Results: The rate of relaxation following washout of KCl was reduced in A-CRF rats vs. controls in the thoracic aorta (P < 0.01), abdominal aorta (P < 0.05), and common carotid artery (P < 0.05), but not in the common femoral artery. Relaxation rates of thoracic aortas increased (P < 0.01), but were not normalized, in response to washout of KCl with Ca2+ -free buffer. Microarray and qRT-PCR analyses of genes involved in excitation-contraction coupling identified 10 genes, which showed significantly altered expression in A-CRF thoracic aortas. At the protein level, the α2 subunit of the Na,K-ATPase (P < 0.001) and SERCA2 (P < 0.05) was significantly downregulated, whereas stromal interaction molecule 1 and calsequestrin-1 and calsequestrin-2 were significantly upregulated (P < 0.05).
Conclusions: Rats with A-CRF show a marked alteration in relaxation of larger conduit arteries localized proximal to the common femoral artery. This abnormality may be caused by reduced cytosolic Ca2+ clearance in vascular smooth muscle cells secondary to dysregulation of proteins crucially involved in this process.
Keywords: aorta; chronic kidney disease; excitation-contraction coupling; hypertension; microarray.
© 2016 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.