Increased expression of endothelin-1 and inducible nitric oxide synthase isoform II in aging arteries in vivo: implications for atherosclerosis.
We here report that aging increases expression of endothelin-1 and NO synthases in the vasculature and kidney of normotensive rats in vivo. Expression of preproendothelin-1 mRNA was quantified by RT-PCR and in situ hybridization, and endothelin-1 protein was determined by radioimmunoassay/HPLC. Vascular mRNA expression of NO synthase isoforms II and III was analyzed by RT-PCR. In young animals, vascular endothelin-1 protein was differentially expressed (aorta < renal artery < carotid artery) and increased with aging in all vascular beds (P < 0.05). In the intact aorta of aged rats, mRNA expression of preproendothelin-1, "inducible" NO synthase II, and endothelial cell NO synthase III gene was up-regulated (P < 0.05). Moreover, preproendothelin-1 mRNA expression increased in glomeruli and tubulointerstitial cells (P < 0.05). To our knowledge this is the first study demonstrating local vascular up-regulation of the trophic factor endothelin under physiological conditions. Activation of vascular endothelin and NO synthases may be important, pressure-independent factors contributing to structural and functional abnormalities of age-dependent diseases, including atherosclerosis.
Goettsch
W
W
Institute of Pathophysiology, Faculty of Medicine, Martin Luther University, D-06097 Halle, Germany.
Lattmann
T
T
Amann
K
K
Szibor
M
M
Morawietz
H
H
Münter
K
K
Müller
S P
SP
Shaw
S
S
Barton
M
M
D000375:Aging / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001158:Arteries / Q000378:metabolism*; D001161:Arteriosclerosis / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D019332:Endothelin-1 / Q000235:genetics*; D016232:Endothelins / Q000235:genetics; D015870:Gene Expression; D006801:Humans; D017403:In Situ Hybridization; D007668:Kidney / Q000378:metabolism; D008297:Male; D019001:Nitric Oxide Synthase / Q000235:genetics*; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D011498:Protein Precursors / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011921:Rats, Inbred WKY
D019332:Endothelin-1; D016232:Endothelins; D011498:Protein Precursors; D012333:RNA, Messenger; C496319:NOS2 protein, human; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496318:Nos2 protein, rat; C496316:Nos3 protein, rat