Raised vascular calcium in an animal model: effects on aortic function.
STUDY OBJECTIVE - The aim of the study was to develop an animal model to study the relationships between raised tissue calcium and vascular function. DESIGN - Ectopic calcification was developed in the animal model using chronic vitamin D2 intoxication, after which functional studies were performed in isolated superfused aortic rings. Results were compared with control preparations. EXPERIMENTAL ANIMALS - 160 female Sprague-Dawley rats weighing 200-225 g were randomly divided into experimental (vitamin D2 1 mg.d-1) and control (vehicle only) groups. MEASUREMENTS and RESULTS - Aortas from vitamin D treated animals had a higher calcium content than control aortas, without concomitant increases in cardiac calcium. Aortas with high calcium content were found to develop greater tension than control aortas when exposed to noradrenaline in the absence of extracellular calcium, but the tension maxima achieved in response to noradrenaline in calcium containing media or to high potassium depolarising solution were the same. The rate of development of contraction in response to noradrenaline was greater in aortas from the vitamin D treated animals than in controls. Isoprenaline and sodium nitroprusside produced less relaxation in the animal model aortas than in the controls. CONCLUSIONS - The results suggest that increased aortic calcium affects the response of the tissue to vasoactive agents. It appears that the additional vascular calcium may be stored in an agonist releasable pool, probably within the sarcoplasmic reticulum. The enlarged or newly developed pools appear to be refillable from the extracellular medium but not by intracellular reuptake of calcium, suggesting a bicompartmental model of intracellular calcium release and reuptake.
Cannon
E P
EP
Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston 77550.
Williams
B J
BJ
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D002114:Calcinosis / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology*; D002118:Calcium / Q000378:metabolism; D009202:Cardiomyopathies / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology*; D004195:Disease Models, Animal; D004872:Ergocalciferols; D005260:Female; D007545:Isoproterenol / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D004872:Ergocalciferols; D007545:Isoproterenol; D002118:Calcium; D009638:Norepinephrine