Vascular calcium overload produced by administration of vitamin D3 and nicotine in rats. Changes in tissue calcium levels, blood pressure, and pressor responses to electrical stimulation or norepinephrine in vivo.
Increased calcium content of cardiovascular tissues is a phenomenon common to natural aging and various pathological conditions such as hypertension and arteriosclerosis. We investigated an accelerated cardiovascular calcium overload model in young rats produced by treatment with a single dose of vitamin D3 (300,000 IU/kg, i.m.) followed by up to 4 days of twice daily doses of nicotine (25 mg/kg, p.o.). Large increases in the calcium content of the aorta, kidneys, and myocardium but not in the liver or brain were seen. The magnesium content of these tissues was not modified. On the day following the last nicotine injection, there was marked cardiovascular calcium overloading, the aortic calcium level increasing by up to nine times that of controls. The animals had lower body weights, however, and there was a significant degree of mortality (up to 42%). Signs of kidney failure were evident; the blood urea level, for instance, was doubled. If rats were allowed 13 or 180 days to recover, they showed normal growth and kidney function; aortic calcium overload was still pronounced: 16- and 7-fold increases, respectively. Cardiovascular function in recovery animals was characterized by a doubling of pulse pressure. Dose-response curves following noradrenergic stimulation were shifted to the right after 13 (but not after 180) days recovery. Arterial norepinephrine content doubled. The chronic effects of hypervitaminosis D plus nicotine may produce a useful model for the study of the physiological and/or pharmacological consequences of calcium overload.
Laboratoire de Pharmacologie, Faculté des Sciences Pharmaceutiques et Biologiques, Nancy, France.
E
E
Thorin
D
D
Henrion
L
L
Oster
N
N
Thorin-Trescases
C
C
Capdeville
J A
JA
Martin
J M
JM
Chillon
P E
PE
Hicks
J
J
Atkinson
D000375:Aging / Q000502:physiology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D002762:Cholecalciferol / Q000633:toxicity*; D003404:Creatinine / Q000097:blood; D003655:Decerebrate State; D004558:Electric Stimulation; D006339:Heart Rate / Q000187:drug effects; D008274:Magnesium / Q000378:metabolism; D008297:Male; D008903:Minerals / Q000032:analysis / Q000494:pharmacology; D009538:Nicotine / Q000633:toxicity*; D009638:Norepinephrine / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D013116:Spinal Cord / Q000502:physiology; D013564:Sympathetic Nervous System / Q000187:drug effects; D014508:Urea / Q000097:blood
D008903:Minerals; D002762:Cholecalciferol; D009538:Nicotine; D014508:Urea; D003404:Creatinine; D008274:Magnesium; D002118:Calcium; D009638:Norepinephrine