Effect of AT₁ receptor blockade on cardiac apoptosis in angiotensin II-induced hypertension

Abstract

sc) for 7 days with or without the AT1 receptor antagonist losartan (10 mg ⅐ kg Ϫ1 ⅐ day Ϫ1 orally). Cardiac function was assessed by echocardiography. Apoptosis in the heart was detected and quantified by in situ TdT-mediated dUTP nickend labeling (TUNEL) and radiolabeled DNA laddering. Expression of bax, bcl-2, caspase 3, and AT1 and AT2 receptors was examined by Western blot analysis. Activity of caspase 3 was also measured by a fluorometric immunosorbent enzyme assay. Tail cuff systolic blood pressure was elevated (P Ͻ 0.01, n ϭ 6) in ANG II-infused rats (173 Ϯ 3 mmHg) versus controls (111 Ϯ 2 mmHg) and reduced by losartan (134 Ϯ 4 mmHg). Cardiac function was essentially unchanged in ANG II-infused rats. Increased internucleosomal DNA cleavage by TUNEL assay and radiolabeled DNA laddering showed results compatible with enhanced cardiomyocyte apoptosis in the hearts of ANG-II infused rats. The bax-to-bcl-2 ratio, expression of the active form of caspase 3 (17 kDa), and activity of caspase 3 in the hearts of the ANG II group increased more than twofold above controls. Protein expression of AT1 and AT2 receptors was significantly increased in ANG II-infused rats compared with control rats. Losartantreated ANG II-infused rats exhibited normalized apoptosis, bax, caspase 3 activity, and AT1 receptors. ANG II stimulation of AT1 receptors in the heart in vivo is associated with an increased rate of apoptosis without major hemodynamic consequences. Bax and caspase 3 are involved in the apoptotic signaling pathway in this experimental paradigm.caspase; bax; bcl-2

A positive feedback loop of phosphodiesterase 3 (PDE3) and inducible cAMP early repressor (ICER) leads to cardiomyocyte apoptosis

“…In addition, cardiomyocyte apoptosis measured by TUNEL-positive cells was also significantly increased in adult myocytes in vivo after Ang II infusion (Fig. 1B), consistent with previous findings in Ang II infused animals (16). We also observed a time-dependent downregulation of PDE3A in rat heats with Ang II infusion for 1, 3, and 7 days (Fig.…”

Alpinate Oxyphyllae Fructus (Alpinia Oxyphylla Miq) Extracts Inhibit Angiotensin-II Induced Cardiac Apoptosis in H9c2 Cardiomyoblast Cells

“…Angiotensin II (Ang II) plays an important role in cardiovascular diseases such as hypertension, atherosclerosis, left ventricular hypertrophy (LVH), and heart failure. [4][5][6][7][8][9][10] Most studies indicate that Ang II induces cardiovascular hypertrophy, cardiac apoptosis, mitochondrial dysfunction, and cardiac remodeling through Ang II type 1 receptor (AT1R) activation, 4,7,11,12) but an opposing theory posits that this occurs via AT2R. [13][14][15][16][17] Although the functions of these two major Ang II receptors are ambiguous, the harm Ang II does cardiomyocytes is certain.…”

“…[13][14][15][16][17] Although the functions of these two major Ang II receptors are ambiguous, the harm Ang II does cardiomyocytes is certain. 10,[18][19][20] In cardiac hypertrophy, the phosphatase calcineurin, which is calcium-dependent, dephosphorylates, transcription factor NFAT3 and causes it to translocate to the nucleus. 21) The atrial natriuretic peptide (ANP) and b-type natriuretic peptide (BNP) are then overexpressed.…”

Recombinant adeno-associated virus-mediated human kallikrein gene therapy protects against hypertensive target organ injuries through inhibiting cell apoptosis

“…Increased cardiomyocyte apoptosis has been recently demonstrated in SHRs and patients with essential hypertension [12] . Although apoptosis could be induced by pressure overload, in vitro and in vivo findings indicated that angiotensin II could be critical in cardiac apoptosis [13,14] . A study of patients with essential hypertension by González and his colleagues indicated that the efficacy of antihypertensive treatment in reducing blood pressure does not predict its capacity to reduce myocardial apoptosis in hypertensive patients [15] .…”