Chronic stress induces rapid occlusion of angioplasty-injured rat carotid artery by activating neuropeptide Y and its Y1 receptors.
OBJECTIVE
We reported previously that neuropeptide Y (NPY) induces an atherosclerotic-like lesion that is significantly reduced by NPY-Y1 and NPY-Y5 receptor (R) inhibitors. Because antagonists also inhibit neointima induced by angioplasty alone, we now test whether stress-induced endogenous NPY release mimic these changes.


RESULTS
Rats were nonstressed or stressed (4 degrees C water; 2 hours per day for 14 days) starting immediately before and continuing after carotid artery angioplasty. Stress acutely and chronically increased blood pressure and doubled plasma NPY levels. After 14 days, angioplasty-induced neointima was markedly greater in stressed (than nonstressed) rats, in which most of the vessels became occluded with an atherosclerotic-like lesion containing macrophages, lipids, thrombus, and microvessels that was similar but more inflammatory than the injury in the NPY-treated vessels. Fourteen days after angioplasty combined with stress or NPY, Y1R and Y5R (mRNA and protein) became upregulated in areas of neointima, microvessels, and macrophages in injured carotid arteries. Stress- and NPY-induced changes were completely prevented by a selective Y1R antagonist (0.02 micromol/kg per minute for 14 days), whereas neointima induced by angioplasty alone was reduced by 60%.


CONCLUSIONS
Because of sympathetic NPY release, stress may be a less-than-appreciated risk factor for restenosis/atherosclerosis, and Y1R antagonists a potential therapy for these conditions.
Li
Lijun
L
Department of Physiology and Biophysics, Georgetown University Medical Center, Washington, DC, USA.
Jönsson-Rylander
Ann-Cathrine
AC
Abe
Ken
K
Zukowska
Zofia
Z
D000800:Angioplasty, Balloon / Q000009:adverse effects*; D000818:Animals; D001794:Blood Pressure; D002340:Carotid Artery Diseases / Q000453:epidemiology / Q000378:metabolism / Q000628:therapy; D020212:Carotid Artery Injuries / Q000453:epidemiology / Q000378:metabolism*; D016893:Carotid Stenosis / Q000453:epidemiology / Q000378:metabolism* / Q000628:therapy; D002908:Chronic Disease; D003080:Cold Temperature; D008297:Male; D009478:Neuropeptide Y / Q000097:blood*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D017476:Receptors, Neuropeptide Y / Q000235:genetics* / Q000378:metabolism; D012008:Recurrence; D012307:Risk Factors; D013312:Stress, Physiological / Q000453:epidemiology / Q000378:metabolism*; D013564:Sympathetic Nervous System / Q000378:metabolism / Q000502:physiology; D017539:Tunica Intima / Q000378:metabolism; D017540:Tunica Media / Q000378:metabolism
D009478:Neuropeptide Y; D012333:RNA, Messenger; D017476:Receptors, Neuropeptide Y; C097212:neuropeptide Y-Y1 receptor; C100568:neuropeptide Y5 receptor