Systemic Up-Regulation of Angiotensin II Type 1 Receptor in Cardiac Donors with Spontaneous Intracerebral Hemorrhage

Yamani, Mohamad H.; Cook, Daniel; Tuzcu, E. Murat; Abdo, Ashraf; Paul, Philip; Ratliff, Norman B.; Yu, Yang; Yousufuddin, Mohammad; Feng, Jing; Hobbs, Robert E.; Rincón, Gustavo; Bott‐Silverman, Corinne; McCarthy, Patrick M.; Young, James B.; Starling, Randall C.

doi:10.1111/j.1600-6143.2004.00463.x

Cited by 21 publications

(10 citation statements)

References 15 publications

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“…Therefore, it is conceivable to assume that the inhibition of central AT1R can considerably contribute to the observed beneficial effects of the telmisartan on neurological outcome of ICH. In a study involving heart transplantation donors, the systemic up-regulation of AT1R was documented with the subsequent development of transplant vasculopathy and ICH (Yamani et al, 2004). The increased AT1R expression in the hemorrhagic brain, as was documented in our study, suggests its patho- Fig.…”

Section: Therapeutic Effect Of Telmisartan On Ichmentioning

confidence: 81%

Blockade of AT1 Receptor Reduces Apoptosis, Inflammation, and Oxidative Stress in Normotensive Rats with Intracerebral Hemorrhage

Jung

Chu²,

Lee³

et al. 2007

J Pharmacol Exp Ther

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Angiotensin II exerts its central nervous system effects primarily via its receptors AT1 and AT2, and it participates in the pathogenesis of ischemia via AT1. The selective AT1 receptor blocker (ARB) is used in the hypertension treatment, and it exerts a variety of pleiotropic effects, including antioxidative, antiapoptotic, and anti-inflammatory effects. In this study, we investigated the therapeutic effect of the ARB telmisartan in experimental intracerebral hemorrhage (ICH) in normotensive rats. ICH was induced via the collagenase infusion or autologous blood injection. Either telmisartan at 30 mg/kg/dose or phosphate-buffered saline was orally administered 2 h after ICH induction. We evaluated hemorrhage volume, brain water content, and functional recovery, and we performed the histological analysis for terminal deoxynucleotidyl transferase dUTP nick-end labeling, leukocyte infiltration, and microglia activation. A variety of intracellular signals, in terms of oxidative stress, apoptotic molecules, and inflammatory mediators, were also measured. Telmisartan reduced hemorrhage volume, brain edema, and inflammatory or apoptotic cells in the perihematomal area. Telmisartan was noted to induce the expression of endothelial nitric-oxide synthase and peroxisome proliferatoractivated receptor ␥ and decrease oxidative stress, apoptotic signal, tumor necrosis factor-␣, and cyclooxygenase-2 expression. The telmisartan-treated rats exhibited less pronounced neurological deficits and recovered better. Thus, telmisartan seems to offer neural protection, including antiapoptosis, antiinflammatory, and antioxidant benefits in the intracerebral hemorrhage rat model. Angiotensin II is a potent vasoconstrictor hormone that is cleaved from angiotensinogen by renin and angiotensin-converting enzyme. In addition to its known vital role in both cardiovascular and fluid homeostasis, several lines of evidence implicate angiotensin II in the ischemic neuronal injury via the angiotensin II receptor subtype AT1 (AT1R) (Walther et al., 2002). Emerging evidence suggest that peripherally administered AT1R blockers (ARBs) can interact with AT1R in the brain across the blood-brain barrier (BBB) and reduce the infarct volumes in the experimental cerebral ischemia model (Dai et al., 1999;Nishimura et al., 2000;Yamakawa et al., 2003). Recently, ARBs were also proven to attenuate inflammatory and oxidative stress (Ando et al., 2004;Zhou et al., 2005) and to regulate the nitric-oxide synthase isoenzymes in the brain (Ito et al., 2002). As a potent and highly selective AT1 receptor antagonist, telmisartan (TMS) is described chemically as 4[(1,4-dimethyl-2-propyl[2,6-bi-1H-benzimidazol]-1-yl)methyl] [1,1-biphenyl]-2-carboxylic acid. This unique feature of telmisartan accounts for both its high receptor affinity and its excellent pharmacokinetic properties. Furthermore, telmisartan could

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Section: Therapeutic Effect Of Telmisartan On Ichmentioning

confidence: 81%

Blockade of AT1 Receptor Reduces Apoptosis, Inflammation, and Oxidative Stress in Normotensive Rats with Intracerebral Hemorrhage

Jung

Chu²,

Lee³

et al. 2007

J Pharmacol Exp Ther

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“…Furthermore, biopsied hearts from non-ICH donors developed less fi brosis and coronary artery disease, as demonstrated by smaller ultrasonographic vessel intimal thickness. The same group also found signifi cant upregulation in mRNAexpressing angiotensin II type 1 receptor, a marker of acute infl ammation, in the transplanted hearts of patients who died of ICH as compared with donors who died of trauma [30]. Infl ammation also may play a role in the pathogenesis of ventricular arrhythmia in patients with SAH.…”

Section: Pathophysiologymentioning

confidence: 91%

Neurogenic stunned myocardium

Nguyen

Zaroff

2009

Curr Neurol Neurosci Rep

143

126

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Neurogenic stunned myocardium may be defined as myocardial injury and dysfunction occurring after diverse types of acute brain injury as a result of imbalance of the autonomic nervous system. The spectrum of observed cardiac abnormalities includes electrocardiographic changes, arrhythmia, myocardial necrosis, release of B-type natriuretic peptide, and both systolic and diastolic dysfunction of the left ventricle. These are reversible abnormalities, and although management should include careful cardiac monitoring, treatments should generally focus on the underlying neurologic process to maximize neurologic recovery.

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“…The following probes and primers for human genes were used: GAPDH (forward, 5′-GAAGGTGAAGGTCGGAGT-3′; reverse, 5′-GAAGATGGTGATGGGATTTC-3′; probe, 5′-FAM-CAAGCTTCCCGTTCTCAGCC-TAMRA-3′) [18], angiotensinogen (forward, 5′-TCTCCCCGGACCATCCA-3′; reverse, 5′-TGCTCAATTTTTGCAGGTTCAG-3′; probe, 5′-6-FAM-CCATGCCCCAACTGGTGCTGC-TAMRA-3′) [19], angiotensin II type 1 receptor (AT1R; forward, 5′-AGCCAAATCCCACTCAAACCT-3′; reverse, 5′-TCGAACATGTCACTCAACCTCA-3′; probe, 5′-FAM-ATCCACCAAGAAGCCTGCACACCATGTTT-TAMRA-3′) [20], angiotensin II type 2 receptor (AT2R; forward, 5′-AAGTCCTGAAGATGGCAGCTG-3′; reverse, 5′-CAGGTCAATGACTGCTATAACTTCG-3′; probe, 5′-FAM-CTGGCCTTCATCATTTGGTGCCTTCC-TAMRA-3′) [20], (pro)renin receptor (forward, 5′-AGATGACATGTACAGTCTTTATGGTGG-3′; reverse, 5′-TGCTGGGTTCTTCGCTTGT-3′; probe, 5′-FAM-TTTGACACCTCCCTCATTAGGAAGACAAGGACT-TAMRA-3′) [21], angiotensin-converting enzyme (ACE; forward, 5′-TGCCTATCCTTCCTATATCAGTCCAA-3′; reverse, 5′-TTGTCCAAAATCTACCCCACATATC-3′; probe, 5′-FAM-ATGCCTCCCTGCTCATTTGCTTGGT-TAMRA-3′) [22], and ACE2 (forward, 5′-CATTGGAGCAAGTGTTGGATCTT-3′; reverse, 5′-GAGCTAATGCATGCCATTCTCA-3′; probe, 5′-FAM-CTTGCAGCTACACCAGTTCCCAGGCA-TAMRA-3′) [23]. Probes and primers for the human genes encoding renin and neprilysin were purchased from the Applied Biosystems Custom TaqMan Gene Expression Assay service (Foster City, Calif., USA).…”

Section: Methodsmentioning

confidence: 99%

Association of (Pro)renin Receptor mRNA Expression with Angiotensin-Converting Enzyme mRNA Expression in Human Artery

Takemitsu

Ichihara²,

Kaneshiro³

et al. 2009

Am J Nephrol

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Background/Aims: A significant role of (pro)renin receptor in the pathogenesis of end-organ damage has been suggested only in animal studies. This study was conducted to examine the mRNA expression of (pro)renin receptor in human artery. Methods: In 141 kidney failure patients, the mRNA was harvested from arterial fragments obtained during surgery constructing an arteriovenous access for hemodialysis therapy, and expression levels of (pro)renin receptor and other components of the renin-angiotensin system were determined. Results: Arterial (pro)renin receptor expression was similar in diabetic and non-diabetic patients, although plasma prorenin levels were significantly higher in the diabetic patients than in the non-diabetic patients. The arterial (pro)renin receptor mRNA levels of the hypertensive patients, who had not been treated with either angiotensin-converting enzyme (ACE) inhibitors or angiotensin II type 1 receptor blockers, were significantly lower than those of the patients who had been treated with either drug. Multiple regression analyses showed a significant association with a large coefficient between the arterial mRNA level of the (pro)renin receptor and the arterial mRNA level of ACE; this significant association disappeared in patients who had been treated with either drug. Conclusion: (Pro)renin receptor may contribute to the generation of arterial angiotensin II in kidney failure patients.

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Systemic Up-Regulation of Angiotensin II Type 1 Receptor in Cardiac Donors with Spontaneous Intracerebral Hemorrhage

Cited by 21 publications

References 15 publications

Blockade of AT1 Receptor Reduces Apoptosis, Inflammation, and Oxidative Stress in Normotensive Rats with Intracerebral Hemorrhage

Blockade of AT1 Receptor Reduces Apoptosis, Inflammation, and Oxidative Stress in Normotensive Rats with Intracerebral Hemorrhage

Neurogenic stunned myocardium

Association of (Pro)renin Receptor mRNA Expression with Angiotensin-Converting Enzyme mRNA Expression in Human Artery

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