Angiotensin II Receptor mRNA Expression and Vasoconstriction in Human Coronary Arteries: Effects of Heart Failure and Age

Abstract

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 Ω0.31, PϽ0.05). Also, the AT 1 receptor mRNA expression levels decreased with increasing age in patients with heart failure (r 2 Ω0.74, PϽ0.05), while no such correlation could be shown in the control group (r 2 Ω0.04, PΩn.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.

Increased perfusion pressure enhances the expression of endothelin (ETB) and angiotensin II (AT1, AT2) receptors in rat mesenteric artery smooth muscle cells

“…This was largely expected, since it was unlikely for translation to have had enough time to produce suffi cient amounts of fi nished protein structure at this time. The of these receptors seen in heart failure and ischemic heart disease (14,15).…”

“…D16840) were designed as follows: it might contribute to pathological vasomotor function. The AT 1 -and AT 2 -receptors have been shown to be down-regulated in heart failure (14) and the AT 1 -receptor was also reduced in ischemic heart disease (15). The data regarding the regulation of ET-1 synthesis and release by shear stress forces on endothelial cells are controversial, since some reports have described a shear stress-dependent induction of ET-1 production, others have found no signifi cant changes in the ET-1 release, and still others have shown down-regulation.…”

Increased expression of vascular endothelin type B and angiotensin type 1 receptors in patients with ischemic heart disease

“…The levels of expression were even higher in arteries from patients undergoing CABG surgery. The plasma level of angiotensin II is known to be elevated in different heart conditions, such as heart failure [ 28 ], hypertension [ 29 ], hypoxia [ 30 ], hypercholesterolemia [ 31 ] and hyperglycemia [ 32 ]. We have found, herein, that this may be associated with enhanced expression of vascular angiotensin II receptors.…”

“…Plasma levels of ET-1 and angiotensin II are elevated during CABG surgery [ 18 ]. Both endothelin and angiotensin II receptors have been shown to mediate strong vasoconstrictor effects in bypass grafts [ 28 ]. Many measures have been undertaken to control the vessel tone during surgery, including dilating the vessels with potent vasodilators such as papaverine, sodium nitroprusside and nifedipine, or mechanically distending the vessels with saline.…”

Angiotensin‐(1‐7): Pharmacology and New Perspectives in Cardiovascular Treatments

“…It is well documented that Ang II promotes cell proliferation (Daemen et al 1991;Su et al 1998) and vasoconstriction (Wackenfors et al 2004), whereas Ang-(1-7) has antiproliferative actions on cardiac myocytes (Tallant et al 2005) and vascular smooth muscle (Strawn et al 1999), and is a vasodilator . These actions have uncovered a new way to think about the RAS, both conceptually and therapeutically.…”