Aging differentially modifies arterial sensitivity to endothelin-1 and 5-hydroxytryptamine: studies in dog coronary arteries and rat arterial mesenteric bed.
The influence of age on vascular reactivity to endothelin-1 (ET-1) and 5-hydroxytryptamine (5-HT) was studied in coronary artery rings from dogs of 9 years of age or younger, and dogs older than 9 years. ET-1 caused concentration-dependent contractions that developed about 100% of the 70 mM KCl-induced tension in the younger dogs; those from older dogs did not generate more than 20%. In contrast, 5-HT developed only about 20% of the KCl-induced tension in rings from young dogs, whereas in the older animals, it developed up to 120% of the KCl tension. No significant difference in the tension developed by 70 mM KCl was noted between both groups of dogs. Mechanical denudation of the endothelial cell layer caused a modest, yet significant, leftward shift of the ET-1 and 5-HT concentration-response curves only in the younger dogs. N omega-Nitro-L-arginine (15 microM) shifted the ET-1 concentration-response curves to the left in rings from both groups of dogs. Rings precontracted with 20 mM KCl relaxed in a concentration-dependent fashion with acetylcholine; its sensitivity was about threefold less in the older group of dogs. To validate the changes in vascular reactivity with age, a parallel study was performed perfusing the arterial mesenteric bed of rats of 3, 7, and 30 weeks of age. In this experimental model, the efficacy of ET-1 significantly decreased with age and that of 5-HT was significantly increased. The vasomotor reactivity of noradrenaline was modestly affected by aging, whereas the acetylcholine-induced vasorelaxation was significantly reduced with age.
Donoso
M V
MV
Dept. de Fisiología, Facultad de Ciencias Biológicas P. Universidad Católica de Chile, Santiago.
Fournier
A
A
Peschke
H
H
Faúndez
H
H
Domenech
R
R
Huidobro-Toro
J P
JP
D000109:Acetylcholine / Q000494:pharmacology; D000375:Aging / Q000502:physiology*; D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects* / Q000254:growth & development / Q000502:physiology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D016232:Endothelins / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000502:physiology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000254:growth & development / Q000502:physiology; D009119:Muscle Contraction / Q000187:drug effects*; D024510:Muscle Development; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000254:growth & development / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology; D009928:Organ Specificity; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D012701:Serotonin / Q000494:pharmacology*
D016232:Endothelins; D012701:Serotonin; D011189:Potassium Chloride; D000109:Acetylcholine; D009638:Norepinephrine