Effect of chronic treatment with the calcium entry blocker, isradipine, on vascular calcium overload produced by vitamin D3 and nicotine in rats.
Treatment of young rats with vitamin D3 and nicotine produced a 35-fold increase in the calcium content of the aorta and a 4-fold increase in the calcium content of the mesenteric arterial bed. Blood pressure was not modified. In vitro, aortic rings and mesenteric arterial bed preparations from such animals showed diminished vasoconstrictor responses to norepinephrine. After precontraction with norepinephrine, the endothelium-dependent vasodilator, carbachol, produced vasorelaxation. This latter effect was attenuated in aortic rings and mesenteric arterial bed preparations from animals previously treated with vitamin D3 and nicotine, but the vasodilator effect of sodium nitroprusside (which is independent of the endothelium) was unchanged. Prolonged treatment with the calcium entry blocker, isradipine, at a dose (1 mg/kg, i.p.) which had no effect on blood pressure, prevented calcium overload of the mesenteric arterial bed, but did not modify aortic calcium overload. Isradipine treatment had no effect on vasoconstrictor responses to norepinephrine in vitro. Such treatment did, however, restore the endothelium-dependent vasodilator effect of carbachol in the mesenteric arterial bed (but not in aortic rings). In conclusion, in a rat model of vascular calcium overload produced by administration of vitamin D3 plus nicotine, chronic treatment with a low dose of the calcium entry blocker, isradipine, restored the endothelium-dependent vasorelaxant effect of carbachol in the mesenteric arterial bed, but not in the aorta.
Henrion
D
D
Laboratoire de Pharmacologie Cardio-vasculaire, Faculté de Pharmacie de l'Université de Nancy I, France.
Chillon
J M
JM
Capdeville-Atkinson
C
C
Atkinson
J
J
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002118:Calcium / Q000097:blood / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002762:Cholecalciferol / Q000494:pharmacology*; D004095:Dihydropyridines / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects; D017275:Isradipine; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000378:metabolism; D008954:Models, Biological; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D009538:Nicotine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D002762:Cholecalciferol; D009538:Nicotine; D002118:Calcium; D017275:Isradipine