Angiotensin-(1–7) prevents diabetes-induced cardiovascular dysfunction

2007 ◽  
Vol 292 (1) ◽  
pp. H666-H672 ◽  
Author(s):  
Ibrahim F. Benter ◽  
Mariam H. M. Yousif ◽  
Constantin Cojocel ◽  
May Al-Maghrebi ◽  
Debra I. Diz
Keyword(s):  
Therapeutic Strategy ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Diabetic Patients ◽  
Cardiovascular Dysfunction ◽  
Urine Protein ◽  
Cardiac Recovery ◽  
Vascular Responsiveness ◽  
Perfused Hearts ◽  
Vasoactive Agonists

The aim of this study was to test the hypothesis that treatment with angiotensin-(1–7) [ANG-(1–7)] or ANG-(1–7) nonpeptide analog AVE-0991 can produce protection against diabetes-induced cardiovascular dysfunction. We examined the influence of chronic treatment (4 wk) with ANG-(1–7) (576 μg·kg−1·day−1 ip) or AVE-0991 (576 μg·kg−1·day−1 ip) on proteinuria, vascular responsiveness of isolated carotid and renal artery ring segments and mesenteric bed to vasoactive agonists, and cardiac recovery from ischemia-reperfusion in streptozotocin-treated rats (diabetes). Animals were killed 4 wk after induction of diabetes and/or treatment with ANG-(1–7) or AVE-0991. There was a significant increase in urine protein (231 ± 2 mg/24 h) in diabetic animals compared with controls (88 ± 6 mg/24 h). Treatment of diabetic animals with ANG-(1–7) or AVE-0991 resulted in a significant reduction in urine protein compared with vehicle-treated diabetic animals (183 ± 16 and 149 ± 15 mg/24 h, respectively). Treatment with ANG-(1–7) or AVE-0991 also prevented the diabetes-induced abnormal vascular responsiveness to norepinephrine, endothelin-1, angiotensin II, carbachol, and histamine in the perfused mesenteric bed and isolated carotid and renal arteries. In isolated perfused hearts, recovery of left ventricular function from 40 min of global ischemia was significantly better in ANG-(1–7)- or AVE-0991-treated animals. These results suggest that activation of ANG-(1–7)-mediated signal transduction could be an important therapeutic strategy to reduce cardiovascular events in diabetic patients.

scholarly journals Reducing Cardiac Injury during ST-Elevation Myocardial Infarction: A Reasoned Approach to a Multitarget Therapeutic Strategy

2021 ◽  
Vol 10 (13) ◽  
pp. 2968
Author(s):  
Alessandro Bellis ◽  
Giuseppe Di Gioia ◽  
Ciro Mauro ◽  
Costantino Mancusi ◽  
Emanuele Barbato ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Reperfusion Injury ◽  
Therapeutic Strategy ◽  
Ventricular Remodeling ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
St Elevation Myocardial Infarction ◽  
Ischemic Time ◽  
St Elevation

The significant reduction in ‘ischemic time’ through capillary diffusion of primary percutaneous intervention (pPCI) has rendered myocardial-ischemia reperfusion injury (MIRI) prevention a major issue in order to improve the prognosis of ST elevation myocardial infarction (STEMI) patients. In fact, while the ischemic damage increases with the severity and the duration of blood flow reduction, reperfusion injury reaches its maximum with a moderate amount of ischemic injury. MIRI leads to the development of post-STEMI left ventricular remodeling (post-STEMI LVR), thereby increasing the risk of arrhythmias and heart failure. Single pharmacological and mechanical interventions have shown some benefits, but have not satisfactorily reduced mortality. Therefore, a multitarget therapeutic strategy is needed, but no univocal indications have come from the clinical trials performed so far. On the basis of the results of the consistent clinical studies analyzed in this review, we try to design a randomized clinical trial aimed at evaluating the effects of a reasoned multitarget therapeutic strategy on the prevention of post-STEMI LVR. In fact, we believe that the correct timing of pharmacological and mechanical intervention application, according to their specific ability to interfere with survival pathways, may significantly reduce the incidence of post-STEMI LVR and thus improve patient prognosis.

Abstract 122: Cardiac mTOR Preserves Cardiac Function Following Ex Vivo Ischemia-Reperfusion in Diet-Induced Obese Mice

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Toshinori Aoyagi ◽  
Takashi Matsui
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Cardiac Function ◽  
Glucose Intolerance ◽  
Ex Vivo ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Heart Weight ◽  
Diabetic Patients ◽  
Significant Difference

The risk of heart failure following myocardial infarction is higher in diabetic patients than nondiabetic patients. The mammalian target of rapamycin (mTOR), a key downstream molecule of insulin-phosphoinositide 3-kinase (PI3K)-Akt signaling pathway, plays an important role in cardioprotection. However, the role of cardiac mTOR in ischemic injury in metabolic syndrome has not been well defined. To address this question, we studied the effect of overexpressing cardiac mTOR on cardiac function following ischemia/reperfusion (I/R) in mice with high-fat diet (HFD)-induced obesity. In this study, we used transgenic mice with cardiac-specific overexpression of mTOR (mTOR-Tg) as reported previously. mTOR-Tg and WT mice at 6 weeks old were fed HFD (60% fat by calories) ad libitum for 14 weeks. Control mTOR-Tg and WT mice were fed a normal chow diet (NCD). At 14 weeks after HFD, glucose and insulin tolerance tests demonstrated that HFD generated glucose intolerance and insulin resistance in both mTOR-Tg (n=20) and WT (n=24) mice. Body weight (BW) and heart weight (HW) were significantly higher in HFD mice than SCD mice (p<0.001 for BW in both strains; p<0.001 and p<0.01 for HW/tibia length, WT and mTOR-Tg, respectively) but there was no difference in BW or HW between HFD-mTOR-Tg and HFD-WT mice. Hearts from all four groups were subjected to global I/R (20 min ischemia, 40 min reperfusion) in the ex vivo Langendorff perfusion model. Baseline left ventricular developed pressure (LVDP) was higher in HFD mice than NCD mice in both strains [185.8 ± 10.7 vs. 143.6 ± 5.0 mmHg, HFD-WT (n=11) vs. NCD-WT (n=10) mice, p<0.01; 178.6 ± 10.1 vs. 135.0 ± 6.3, HFD-mTOR-Tg (n=8) vs. NCD-mTOR-Tg (n=11) mice, p<0.01]. Functional recovery after I/R was significantly lower in HFD-WT mice than NCD-WT mice (percent recovery of LVDP, 15.3 ± 5.4 vs. 44.6 ± 6.3 %, HFD-WT vs. NCD-WT mice, p<0.01). Intriguingly, there was no significant difference in LVDP recovery between HFD-mTOR-Tg and NCD-mTOR-Tg mice (36.5±10.8 vs. 58.8±6.0 %, HFD-mTOR-Tg vs. NCD-mTOR-Tg mice, n.s.). These findings suggest that cardiac mTOR is sufficient to substantially limit the metabolic syndrome-induced cardiac dysfunction following I/R in a mouse model of obesity with glucose intolerance and insulin resistance.

Abstract 3889: Persistent Cardioprotection by Regular Ethanol Consumption After Abstention Depends on eNOS but not iNOS Activity After Reperfusion

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Kazuhiro Kaneda ◽  
Masami Miyamae ◽  
Shingo Sugioka ◽  
Chika Okusa ◽  
Yoshitaka Inamura ◽  
...  
Keyword(s):  
Western Blot ◽  
Ischemia Reperfusion ◽  
Ethanol Consumption ◽  
Left Ventricular ◽  
Triphenyltetrazolium Chloride ◽  
Nos Inhibitor ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide ◽  
Perfused Hearts ◽  
Contractile Recovery

We previously found regular ethanol consumption induces cardioprotection against ischemia-reperfusion (I-R) injury with persistent protection after abstention. The mechanism of this continued protection remains unclear. We now determine how long ethanol cardioprotection persists after abstention and whether inducible and/or endothelial nitric oxide synthase (iNOS and eNOS) play a role in this continued cardioprotection. Isolated perfused hearts from control (CTL) and ethanol-treated (ETOH) guinea pigs were subjected to 30 min global ischemia and 120 min reperfusion. ETOH received 5% ethanol in their drinking water for 8 weeks. I-R was performed on ETOH hearts at 0, 4, 7 and 14 days after abstention. To determine whether iNOS and eNOS play a role in this persistent cardioprotection, a NOS inhibitor, L-NAME (100μM) was given before ischemia or during reperfusion. Contractile recovery was monitored by left ventricular developed (LVDP) and end-diastolic (LVEDP) pressures. Infarct size (IS) was determined by triphenyltetrazolium chloride staining. Myocardial iNOS and eNOS were determined by Western blot and immunohistochemically. After I-R, ETOH at 0, 4 and 7, but not 14 days abstention, had significantly higher LVDP (62±5, 64±5, 54±4, 34±3 vs . 26±3 mmHg, respectively), and lower LVEDP (17±6, 21±3, 30±6, 43±1 vs. 59±5 mmHg, respectively) compared to CTL. IS was significantly reduced in ETOH at 0, 4 and 7, but not 14 days abstention, compared to CTL (24±3, 24±2, 30±3, 37±2 vs. 47±3%, respectively). L-NAME given during reperfusion, but not before ischemia, abolished cardioprotection at 0 and 7 days abstention ( IS: 42±3, 45±3%, N.S. vs. CTL, respectively). Western blot analysis demonstrated upregulation of eNOS expression up to 7 days, but not 14 days abstention. Expression of iNOS was reduced at 0 day. eNOS immunoreactivity was greater at 0, 4 and 7 days and iNOS at 14 days, compared to CTL. Chronic cardioprotection against I-R by regular ethanol consumption persists for at least 7 days after abstention. Increased eNOS activity after reperfusion plays a role in this persistent cardioprotection.

Left Ventricular Dysfunction and Blood Glycohemoglobin Levels in Young Diabetics

1991 ◽  
Vol 30 (05) ◽  
pp. 183-188
Author(s):  
A. Aydrner ◽  
A. Oto ◽  
E. Oram ◽  
O. Gedik ◽  
C. F. Bekdik ◽  
...  
Keyword(s):  
Ejection Fraction ◽  
Left Ventricular Function ◽  
Ventricular Function ◽  
Left Ventricular ◽  
Diabetic Patients ◽  
Filling Fraction ◽  
Time To Peak ◽  
Significant Difference ◽  
The Mean ◽  
Hba1c Levels

Left ventricular function including regional wall motion (RWM) was evaluated by 99mTc first-pass and equilibrium gated blood pool ventriculography and glycohemoglobin (HbA1c) blood levels determined by a quantitative column technique in 25 young patients with insulin-dependent diabetes mellitus without clinical evidence of heart disease, and in healthy controls matched for age and sex. Phase analysis revealed abnormal RWM in 19 of 21 diabetic patients. The mean left ventricular global ejection fraction, the mean regional ejection fraction and the mean 1/3 filling fraction were lower and the time to peak ejection, the time to peak filling and the time to peak ejection /cardiac cycle were longer in diabetics than in controls. We found high HbA1c levels in all diabetics. There was no significant difference between patients with and without retinopathy and with and without peripheral neuropathy in terms of left ventricular function and HbA1c levels.

Relation of insulin resistance and left ventricular function and structure in non-diabetic patients with essential hypertension

2005 ◽  
Vol 60 (2) ◽  
pp. 191-198 ◽  
Author(s):  
Harun EVRENGUL ◽  
Dursun DURSUNOGLU ◽  
Asuman KAFTAN ◽  
Fethi KILICASLAN ◽  
Halil TANRIVERDI ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Essential Hypertension ◽  
Left Ventricular Function ◽  
Ventricular Function ◽  
Left Ventricular ◽  
Diabetic Patients

Cardiac responses to insulin-induced hypoglycemia in nondiabetic and intensively treated type 1 diabetic patients

2001 ◽  
Vol 281 (5) ◽  
pp. E1029-E1036 ◽  
Author(s):  
Raymond R. Russell ◽  
Deborah Chyun ◽  
Steven Song ◽  
Robert S. Sherwin ◽  
William V. Tamborlane ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Radionuclide Angiography ◽  
Left Ventricular ◽  
Cardiac Response ◽  
Left Ventricular Ejection ◽  
Diabetic Patients ◽  
Plasma Catecholamine ◽  
Ventricular Ejection Fraction ◽  
Type 1 Diabetic Patients

Insulin-induced hypoglycemia occurs commonly in intensively treated patients with type 1 diabetes, but the cardiovascular consequences of hypoglycemia in these patients are not known. We studied left ventricular systolic [left ventricular ejection fraction (LVEF)] and diastolic [peak filling rate (PFR)] function by equilibrium radionuclide angiography during insulin infusion (12 pmol · kg−1 · min−1) under either hypoglycemic (∼2.8 mmol/l) or euglycemic (∼5 mmol/l) conditions in intensively treated patients with type 1 diabetes and healthy nondiabetic subjects ( n = 9 for each). During hypoglycemic hyperinsulinemia, there were significant increases in LVEF (ΔLVEF = 11 ± 2%) and PFR [ΔPFR = 0.88 ± 0.18 end diastolic volume (EDV)/s] in diabetic subjects as well as in the nondiabetic group (ΔLVEF = 13 ± 2%; ΔPFR = 0.79 ± 0.17 EDV/s). The increases in LVEF and PFR were comparable overall but occurred earlier in the nondiabetic group. A blunted increase in plasma catecholamine, cortisol, and glucagon concentrations occurred in response to hypoglycemia in the diabetic subjects. During euglycemic hyperinsulinemia, LVEF also increased in both the diabetic (ΔLVEF = 7 ± 1%) and nondiabetic (ΔLVEF = 4 ± 2%) groups, but PFR increased only in the diabetic group. In the comparison of the responses to hypoglycemic and euglycemic hyperinsulinemia, only the nondiabetic group had greater augmentation of LVEF, PFR, and cardiac output in the hypoglycemic study ( P < 0.05 for each). Thus intensively treated type 1 diabetic patients demonstrate delayed augmentation of ventricular function during moderate insulin-induced hypoglycemia. Although diabetic subjects have a more pronounced cardiac response to hyperinsulinemia per se than nondiabetic subjects, their response to hypoglycemia is blunted.

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