title: Sensitivity of norepinephrine-evoked vasoconstriction to pertussis toxin in the old rat.
abstract: In male Wistar rats, the in vitro vasoconstrictor response of the perfused tail artery elicited by norepinephrine or serotonin decreased with age (24 mo old vs. 3 mo old), whereas the fluorescent signal (fura 2) produced by intracellular calcium (Ca2+i) mobilization increased. Both vasoconstriction and the increase in intracellular calcium concentration elicited by a high-K+, depolarizing solution were unaffected by aging. Pertussis toxin, a G protein inhibitor, had no effect on vasoconstriction induced by high K+ but diminished vasoconstrictor responses to norepinephrine in 3- and 12-mo-old animals but not in 24-mo-old animals. Pertussis toxin had no effect on Ca2+i mobilization. The sensitivity of receptor activation to pertussis toxin in tail arteries from 24-mo-old animals was restored by pretreatment with the alpha-adrenoceptor antagonist nicergoline. Nicergoline had no effect on vasoconstriction induced by high K+. Plasma norepinephrine concentration rose with age; nicergoline had no effect on this rise. We suggest that aging leads to a decrease in the intracellular G protein-modulated amplification of vasoconstriction produced by receptor activation and that this could be linked to the hyperadrenergic state. Ca2+ sensitivity can be restored by chronic treatment with an alpha-adrenoceptor antagonist.
authors.affiliation: Laboratoire de Pharmacologie Cardio-vasculaire, Universite Henri Poincare, Faculte de Pharmacie, 54001 Nancy Cedex, France.
authors.forename: A
authors.initials: A
authors.lastname: Robert
authors.forename: N N
authors.initials: NN
authors.lastname: Tran
authors.forename: P
authors.initials: P
authors.lastname: Giummelly
authors.forename: J
authors.initials: J
authors.lastname: Atkinson
authors.forename: C
authors.initials: C
authors.lastname: Capdeville-Atkinson
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000375:Aging / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000037:antagonists & inhibitors; D007425:Intracellular Membranes / Q000378:metabolism; D008297:Male; D009530:Nicergoline / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology*; D009994:Osmolar Concentration; D037342:Pertussis Toxin; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
chemical_list: D000317:Adrenergic alpha-Antagonists; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D010566:Virulence Factors, Bordetella; D012701:Serotonin; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D009530:Nicergoline; D002118:Calcium; D009638:Norepinephrine