Increased kinin levels and decreased responsiveness to kinins during aging.
Kinins are vasoactive peptides released from precursors called kininogens, and serum levels of both T- and K-kininogens increase dramatically as rats age. Kinin release is tightly regulated, and here we show that serum kinin levels also increase with age, from 63 +/- 16 nmol/L in young Fisher 344 rats to 398 +/- 102 nmol/L in old animals. Both K- and T-kininogens contribute sequentially to this increase, with the increase in middle-aged animals being driven primarily by K-kininogen, whereas the further augmentation in older rats occurs by increasing T-kininogen. By measuring ERK activation, we show that aorta endothelial cells from old animals are hyporesponsive to exogenous bradykinin. However, if serum kinin levels are experimentally decreased by lipopolysaccharide treatment, then the endothelial response to bradykinin is re-established. These results indicate that serum levels of kinins increase with age, whereas the responsiveness of target cells to kinins is reduced in these same animals.
Pérez
Viviana
V
Instituto de Ciencias Biomedicas, Programa de Biologia Celular y Molecular and Centro FONDAP de Estudios Molcukares de la Celula, Facultdad de Medicina, Universidad Catolica de Chile, Santiago.
Velarde
Victoria
V
Acuña-Castillo
Claudio
C
Gómez
Christian
C
Nishimura
Sumiyo
S
Sabaj
Valeria
V
Walter
Robin
R
Sierra
Felipe
F
D000375:Aging / Q000097:blood / Q000187:drug effects* / Q000378:metabolism*; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D001920:Bradykinin / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D066298:In Vitro Techniques; D007704:Kininogens / Q000378:metabolism; D007705:Kinins / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344
D007704:Kininogens; D007705:Kinins; D008070:Lipopolysaccharides; D048049:Extracellular Signal-Regulated MAP Kinases; D001920:Bradykinin