Alterations by age of calcium handling in rat resistance arteries.
This study investigated the alterations by age of Ca handling in rat small mesenteric arteries. The contractile responses to phenylephrine and caffeine in small mesenteric arteries from young and old rats were studied in Ca -containing and Ca -free medium. In Ca -containing medium the contraction to phenylephrine (100 micro M) but not to caffeine (10 mM) was greater in old than in young rats. Concentration-response curve to phenylephrine was affected to the same extent by nifedipine (1 micro M) in both age groups, whereas ryanodine (20 micro M) decreased the maximal response to phenylephrine only in young rats. These results suggest the participation of intracellular Ca handling on the observed differences by aging. In Ca -free medium, phenylephrine (10 micro M) but not caffeine (10 mM) induced a greater contraction in old than in young animals, corroborating the results obtained in Ca -containing solution. The greater response to phenylephrine observed in old rats cannot be explained by an increase in the inositol 1,4,5-trisphosphate (IP ) formation because the accumulation of inositol phosphates by phenylephrine was not affected by aging. Results obtained in Ca -free medium using caffeine after phenylephrine or vice versa suggest a common intracellular Ca pool. Pretreatment with ryanodine in Ca -free medium almost abolished contractile response to phenylephrine and caffeine in young rats but only partially decreased them in old animals, suggesting an impairment in the Ca -induced Ca release (CICR) mechanism leading to an increase in the stored Ca content. The greater amount of stored Ca could explain the higher contractile response to phenylephrine observed in aged rats. As a consequence of all these changes due to aging, an imbalance between the two Ca release mechanisms from sarcoplasmic reticulum was observed with a major role of Ca induced release by IP at the expense of an impairment of CICR mechanism. This observation will also help explain the results obtained in the presence of extracellular Ca, where phenylephrine induced a greater maximum response in old animals in spite of a decrease in the midrange sensitivity to this agonist.
Rubio
Cristina
C
Departament de Farmacologia, Terapèutica i Toxicologia, Facultat de Medicina, Universitat Autònoma de Barcelona, Spain.
Moreno
Alicia
A
Briones
Ana
A
Ivorra
M Dolores
MD
D'Ocon
Pilar
P
Vila
Elisabet
E
D000375:Aging / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism* / Q000502:physiology; D008297:Male; D008638:Mesenteric Arteries; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014661:Vasoconstriction / Q000187:drug effects
D010656:Phenylephrine; D002110:Caffeine; D002118:Calcium