[Effect of isosorbide dinitrate on vasomotricity-cytosolic calcium coupling during aging in the rat].
Simultaneous measurement of vasomotricity and variations of cytosolic calcium concentrations (mobilisation of intracellular calcium) on a preparation of a normotensive Wistar rat caudal artery allowed analysis of the vasomotricity-cytosolic calcium coupling with respect to age and after administration of isosorbide dinitrate. Vasomotricity was evaluated from changes in perfusion pressure (delta P) of arterial segments perfused at a steady flow state. These segments were exposed to a fluorescent probe, fura 2, the variations of the intensity of emission of which, at wave lengths of 340 and 380 nm, reflect variations in cytosolic calcium concentration (delta R%). The "efficacy" of the vasomotricity-cytosolic calcium coupling was estimated from the delta P/delta R% ratio. In the rat, ageing is accompanied by a reduction in vasomotricity and efficacy of the coupling during noradrenalin stress testing. However, these two parameters recorded during contractions induced by the calcium in a depolarising medium do not change with age. Isosorbide dinitrate reduces vasoconstriction and the delta P/delta R% ratio during noradrenalin stimulation in the young rat. The effect is less pronounced in older rats. Isosorbide dinitrate also reduced the vasomotricity and efficacy of coupling but to a lesser degree during vaso-constriction induced by the calcium in a depolarising medium, without changing the mobilisation of intracellular calcium irrespective of the age of the animals. In conclusion, ageing seems to affect the vasomotricity-cytosolic calcium coupling mainly during receptor stimulation (noradrenalin) rather than during depolarising stimulation (calcium in a depolarising medium). Isosorbide dinitrate acts mainly on the same depolarising stimulation, independent of age.
Oster
L
L
Laboratoire de pharmacologie cardiovasculaire, faculté de pharmacie, Nancy.
Thorin-Trescases
N
N
Atkinson
J
J
Capdeville-Atkinson
C
C
D000375:Aging; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D007548:Isosorbide Dinitrate / Q000494:pharmacology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D014666:Vasomotor System / Q000187:drug effects*
D007548:Isosorbide Dinitrate; D002118:Calcium
Effet du dinitrate d'isosorbide sur le couplage vasoréactivité-calcium cytosolique lors du vieillissement chez le rat.