Sensitivity of norepinephrine-evoked vasoconstriction to pertussis toxin in the old rat.
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.
Robert
A
A
Laboratoire de Pharmacologie Cardio-vasculaire, Universite Henri Poincare, Faculte de Pharmacie, 54001 Nancy Cedex, France.
Tran
N N
NN
Giummelly
P
P
Atkinson
J
J
Capdeville-Atkinson
C
C
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*
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