Angiotensin II receptor mRNA expression and vasoconstriction in human coronary arteries: effects of heart failure and age.
Angiotensin II is a potent vasoconstrictor that is implicated in the pathogenesis of hypertension, heart failure and atherosclerosis. In the present study, angiotensin II receptor mRNA expression levels were quantified by real-time polymerase chain reaction and the vasocontractile responses to angiotensin II were characterised by in vitro pharmacology in endothelium-denuded human coronary arteries. Angiotensin II type 1 (AT(1)) and type 2 (AT(2)) receptor mRNA expression levels were significantly down-regulated in arteries from patients with heart failure as compared to controls. The angiotensin II-induced vasoconstriction diminished with increasing age in patients with heart failure (r(2)=0.31, P<0.05). Also, the AT(1) receptor mRNA expression levels decreased with increasing age in patients with heart failure (r(2)=0.74, P<0.05), while no such correlation could be shown in the control group (r(2)=0.04, P=n.s.). The AT(2) receptor mRNA expression levels did not correlate with age in patients with heart failure or controls. In conclusion, the diminished angiotensin II vasoconstriction with age in heart failure patients is most likely due to a lower density of AT(1) receptors and may result from a longer period of exposure to heart failure in older patients.
Wackenfors
Angelica
A
Division of Experimental Vascular Research, Department of Internal Medicine, Lund University Hospital, SE-221 84 Lund, Sweden. angelica.wackenfors@med.lu.se
Pantev
Emil
E
Emilson
Malin
M
Edvinsson
Lars
L
Malmsjö
Malin
M
D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000804:Angiotensin II / Q000494:pharmacology / Q000502:physiology; D002303:Cardiac Output, Low / Q000209:etiology / Q000378:metabolism; D016022:Case-Control Studies; D003331:Coronary Vessels / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics / Q000378:metabolism*; D044139:Receptor, Angiotensin, Type 2 / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014661:Vasoconstriction / Q000187:drug effects
D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D000804:Angiotensin II