Search PubMed⌕ Search

Biomedical subjects

J L Mehta

Publications and source records attributed to J L Mehta.

At least 55 records · Page 3Linked to original sources
PubMed2001

Different isoforms of tocopherols enhance nitric oxide synthase phosphorylation and inhibit human platelet aggregation and lipid peroxidation: implications in therapy with vitamin E.

BACKGROUND: alpha-Tocopherol has received much attention in the primary and secondary prevention of coronary artery disease. Absence of other isoforms, such as gamma- and delta-tocopherol, in commercial preparations of vitamin E may account for the inconsistent results of clinical trials. Since platelet aggregation is intimately involved in thrombogenesis, the relative effects of alpha-, gamma-, and delta-tocopherol and their combination were examined on human platelet aggregation, lipid peroxidation, and constitutive nitric oxide synthase (cNOS) activity. METHODS AND RESULTS: Human platelets were incubated with the three different isoforms of tocopherol and their combination for 30 minutes, and then ADP-induced platelet aggregation measured. All three isoforms of tocopherol markedly and similarly decreased platelet aggregation in a concentration (120--480 microM)-dependent manner. All three tocopherols also decreased the level of the lipid peroxidation product, malondialdehyde (MDA), and increased NO release (P < 0.05 vs control). These isoforms of tocopherol did not affect cNOS protein expression, but enhanced cNOS phosphorylation in platelets. The combination of three tocopherols in a concentration found in nature was more potent than alpha-, gamma-, or delta-tocopherol alone in this regard. CONCLUSION: These observations suggest that all three major isoforms of tocopherol have a similar effect on human platelet aggregation. The three isoforms appear to attenuate platelet aggregation at least in part via a decrease in free radical generation and an increase in platelet cNOS activity. The combination of tocopherols has a synergistic platelet inhibitory effect. Future clinical trials should concentrate on the combination of these three isoforms of tocopherols.

Analysis of Variance↗
PubMed2000

Oxidized LDL upregulates angiotensin II type 1 receptor expression in cultured human coronary artery endothelial cells: the potential role of transcription factor NF-kappaB.

BACKGROUND: We demonstrated earlier that angiotensin II (Ang II), by AT(1) receptor activation, upregulates oxidized LDL (ox-LDL) endothelial receptor LOX-1 gene expression and uptake of ox-LDL in human coronary artery endothelial cells (HCAECs). In this study, we investigated the regulation of Ang II receptors (AT1R and AT2R) by ox-LDL and the role of the redox-sensitive transcription factor NF-kappaB in this process. METHODS AND RESULTS: HCAECs were incubated with ox-LDL for 24 hours. Ox-LDL (10 to 40 microg protein/mL) upregulated AT1R but not AT2R, mRNA, or protein. Ox-LDL degraded IkappaBalpha in cytoplasm and activated transcription factor NF-kappaB (P65) in HCAEC nuclear extract. Treatment of cells with the antioxidant alpha-tocopherol (10 to 50 micromol/L) attenuated ox-LDL-mediated degradation of IkappaBalpha and activation of NF-kappaB (P65) and inhibited the upregulation of AT1R mRNA and protein. The role of NF-kappaB signal transduction was further examined by use of an NF-kappaB inhibitor, caffeic acid phenethyl ester (CAPE). Pretreatment of cells with CAPE inhibited ox-LDL-mediated degradation of IkappaBalpha and NF-kappaB activation and inhibited ox-LDL-induced upregulation of AT1R expression. Incubation of cells with both ox-LDL and Ang II increased cell injury, measured as cell viability and LDH release, compared with either ox-LDL or Ang II alone. alpha-Tocopherol as well as the specific AT1R blocker CV11974 (candesartan) attenuated the cell-injurious effects of ox-LDL. CONCLUSIONS: These observations suggest an important role of ox-LDL-mediated AT1R upregulation in cell injury. In this process, NF-kappaB activation seems to play a critical role in signal transduction. These findings provide a basis for the use of antioxidants and AT1R blockers in designing therapy of atherosclerosis.

Angiotensin II↗
PubMed2000

Upregulation of LOX-1 expression in aorta of hypercholesterolemic rabbits: modulation by losartan.

Angiotensin-II (Ang-II) enhances the modification of LDL and the expression of its lectin-like receptor (LOX-1) by activating type 1 (AT(1)) receptors. This study was designed to determine the effect of hypercholesterolemia on LOX-1 expression in aorta and its modulation by the AT(1) receptor blocker losartan. Male New Zealand White rabbits were fed regular chow (Control group), chow with 1% cholesterol and 4% peanut oil (HC-diet group), or 1% cholesterol and 4% peanut oil diet plus losartan (25 mg/kg/day) (Losartan + HC-diet group) for 10 weeks. Animal body weight, serum cholesterol levels, and arterial blood pressure were measured. Aortic intimal thickening was quantitated in H&E-stained segments. LOX-1 expression in aortas was examined by immunohistochemistry and semi-quantitative RT-PCR. High-cholesterol diet did not affect body weight, but induced hypercholesterolemia and extensive intimal thickening. Aortas of rabbits in the control group showed a modest LOX-1 expression in the endothelium. Aortic intimal proliferation in HC-diet group was associated with a marked increase in LOX-1 expression (protein and mRNA) in the endothelium and neointima. Treatment with losartan attenuated aortic intimal proliferation and markedly decreased the enhanced LOX-1 expression. Thus high-cholesterol diet induces the upregulation of LOX-1 expression in neointima of aortas of rabbits. Treatment with losartan, an AT(1) blocker, markedly decreases this enhanced LOX-1 expression.

Angiotensin Receptor Antagonists↗
PubMed2000

Antisense to LOX-1 inhibits oxidized LDL-mediated upregulation of monocyte chemoattractant protein-1 and monocyte adhesion to human coronary artery endothelial cells.

BACKGROUND: We have recently demonstrated a lectin-like receptor for oxidized (ox)-LDL (LOX-1) in human coronary artery endothelial cells (HCAECs). This receptor is upregulated by ox-LDL. The present study examined the significance of LOX-1 in monocyte adhesion to HCAECs and endothelial injury in response to ox-LDL. METHODS AND RESULTS: HCAECs were incubated in the presence of antisense oligodeoxynucleotides to the 5'-coding sequence of the human LOX-1 gene (0.5 microm/L). Basal LOX-1 mRNA and protein were suppressed by antisense LOX-1. Ox-LDL-mediated upregulation of LOX-1 was also suppressed by antisense LOX-1. Incubation of HCAECs with ox-LDL (40 microg/mL) for 24 hours markedly increased monocyte chemoattractant protein-1 (MCP-1) mRNA and protein expression as well as monocyte adhesion to HCAECs (P<0.01). After 48 hours of preincubation of HCAECs with antisense LOX-1, ox-LDL-mediated upregulation of MCP-1 and monocyte adhesion to HCAECs both were suppressed (P<0.01), whereas sense LOX-1 had no effect. Whereas antisense or sense LOX-1 alone (both 0.5 nmol/L) did not injure the cells, antisense LOX-1, but not sense LOX-1, reduced ox-LDL-mediated HCAEC injury, determined as LDH release (P<0.01). Activation of mitogen-activated protein kinase (MAPK) may play a critical role in signal transduction in ox-LDL-mediated alteration in MCP-1 expression, since antisense LOX-1, but not the sense LOX-1, completely inhibited the ox-LDL-induced MAPK activation. CONCLUSIONS: These observations with the first use of a specific antisense to human LOX-1 mRNA suggest that LOX-1 is a key factor in ox-LDL-mediated monocyte adhesion to HCAECs.

Cell Adhesion↗
PubMed2000

Relationship of Chlamydia pneumoniae infection to severity of human coronary atherosclerosis.

BACKGROUND: Infection with Chlamydia pneumoniae has been postulated to play a pathogenic role in atherosclerosis. We examined the role of infection with C pneumoniae in relation to the extent of coronary atherosclerosis. METHODS AND RESULTS: Coronary atherosclerosis was graded microscopically on a postmortem basis in a blinded fashion in 60 subjects as mild (n=18) or severe (n=42) atherosclerosis. Serum antibodies to C pneumoniae were measured by microimmunofluorescence test. Paraffin-embedded coronary artery specimens were examined for the presence of chlamydia by use of a genus-specific direct immunofluorescence monoclonal antibody. Frozen coronary artery specimens were examined by immunoperoxidase for the presence of C pneumoniae by use of a specific monoclonal antibody RR-402. Direct immunofluorescence was reactive in 86% of cases with severe atherosclerosis but in only 6% of cases with mild atherosclerosis (P<0.01), whereas immunoperoxidase staining was reactive in 80% and 38% of cases with severe and mild atherosclerosis, respectively (P<0. 01). Elevated IgG and IgA levels against C pneumoniae were not different in cases with severe and mild atherosclerosis (61% and 30% for severe atherosclerosis and 67% and 42% for mild atherosclerosis, respectively). CONCLUSIONS: This study supports the hypothesis that intracellular infection with C pneumoniae may relate to the severity of atherosclerosis in some subjects. Serum antibody titers against C pneumoniae do not differentiate between severe and mild atherosclerosis.

Adult↗
PubMed2000

Seropositivity against Chlamydia pneumoniae in patients with coronary atherosclerosis.

BACKGROUND: Results of therapy in patients with unstable coronary syndromes with antibiotics directed against Chlamydia pneumoniae have been variable, perhaps due to the heterogeneity of patients in these trials. HYPOTHESIS: The aim of the present study was to correlate the severity of coronary artery disease (CAD) with seropositivity against C. pneumoniae prospectively. METHODS: We measured the frequency of seropositivity (IgG levels > or = 1/64 and IgA levels > or = 1/16 against Chlamydia pneumoniae) in 110 patients with CAD and in 49 controls. RESULTS: As expected, traditional CAD risk factors were seen more often in patients with CAD than in controls. Mean values of total cholesterol (184 +/- 52 and 166 +/- 44 mg/dl, respectively) and triglyceride (143 +/- 60 and 112 +/- 63 mg/dl, respectively) in serum were significantly higher in patients with CAD than in controls (both p < 0.04). There were no significant differences between the two groups in serum high-density lipoprotein cholesterol (34 +/- 13 and 32 +/- 14 mg/dl, respectively) and lipoprotein (a) (Lp(a):241 +/- 247 and 223 +/- 263 mg/l, respectively) levels. The rate of IgG seropositivity was 52% (28/54) in patients with stable CAD, 41% (23/56) in patients with unstable CAD, and 35% in controls (p = NS). The rate of IgA seropositivity was 25% (14/54) in patients with stable CAD, 12% (6/49) in patients with unstable angina, and 12% (6/49) in controls (all p = NS). CONCLUSIONS: Only a small percentage of patients with CAD demonstrate seropositivity against Chlamydia pneumoniae. Antibiotic therapy in these selected patients, but not in the remaining patients, may be considered rational. These considerations may underlie the failure to see consistent benefits of antibiotic therapy in patients with CAD.

Analysis of Variance↗
PubMed2000

Modulation of myocardial SOD and iNOS during ischemia-reperfusion by antisense directed at ACE mRNA.

Renin-angiotensin system (RAS) is involved in the regulation of superoxide dismutase (SOD) and nitric oxide (NO) equilibrium, and its modulation protects hearts from ischemic dysfunction. We examined the effect of a new antisense-oligodeoxynucleotides (AS-ODNs) directed at ACE mRNA on SOD and iNOS expression during myocardial ischemia. Sprague-Dawley rats were treated with saline, AS-ODNs, or inverted-ODNs (IN-ODNs), given with liposome DOTAP/DOPE. Hearts were excised and subjected to 25 min of ischemia followed by 30 min of reperfusion. Ischemia-reperfusion in saline-treated hearts resulted in a decrease in the expression of SOD and an increase in the expression of inducible NOS (iNOS) genes concurrently with myocardial dysfunction. AS-ODNs, but not IN-ODNs, protected hearts against functional deterioration, and upregulated SOD expression and inhibited the expression of iNOS. ACE protein expression was decreased in the rat hearts of the AS-ODNs-treated group, but not in the IN-ODNs group. Thus manipulation of RAS with AS-ODNs directed at ACE mRNA can ameliorate cardiac dysfunction and modulate expression of SOD and iNOS at genomic level.

Animals↗
PubMed2000

Carvedilol prevents epinephrine-induced apoptosis in human coronary artery endothelial cells: modulation of Fas/Fas ligand and caspase-3 pathway.

BACKGROUND: Several studies have shown that carvedilol, a multiple action neurohumoral antagonist, reduces mortality in patients with congestive heart failure (CHF). In addition to being a beta-adrenoceptor antagonist, carvedilol is a potent antioxidant. Since there is evidence for elevation of catecholamine levels in plasma and coronary artery endothelial cell injury in CHF, the present study was designed to test the hypothesis that carvedilol inhibits epinephrine-induced apoptosis, and the inhibitory effect is mediated by modulation of Fas, Fas ligand (FasL) and caspase-3 pathway, in cultured human coronary artery endothelial cells (HCAECs). METHODS AND RESULTS: HCAECs were exposed to epinephrine alone, carvedilol + epinephrine, or atenolol + epinephrine for 24 h. Epinephrine increased the number of apoptotic cells, measured by in situ nick end-labeling staining (from 4.2 +/- 1.3% to 28.6 +/- 6.0%, P < 0.01, n = 6) and by DNA laddering on agarose gel electrophoresis. Epinephrine also increased Fas and FasL protein expression (P < 0.01 vs. control, n = 6), and activated intracellular protease caspase-3 (P < 0.01 vs. control, n = 6). These effects of epinephrine were completely inhibited by carvedilol. Atenolol in equimolar concentration also attenuated epinephrine-mediated effects, but the effects of atenolol were less marked than those of carvedilol (P < 0.01). To explore the basis of differential effects of carvedilol and atenolol, effects of these agents on epinephrine-induced lipid peroxidation was measured. Lipid peroxidation was completely blocked by carvedilol, whereas equimolar concentration of atenolol had much less (P < 0.05) effect. CONCLUSION: Epinephrine induces apoptosis in HCAECs, and this effect is associated with activation of Fas-FasL and caspase-3 signal transduction pathway. Carvedilol can, more effectively than atenolol, inhibit these effects of epinephrine. The potent antioxidant effect of carvedilol is probably responsible for the superior effect.

Antioxidants↗
PubMed2000

Inhibition of arterial thrombogenesis by quinapril but not losartan.

The cardioprotective effect of angiotensin converting enzyme (ACE) inhibitors and angiotensin type I (AT1) receptor blockers may relate to their antithrombotic effect. We determined the differential effects of the ACE inhibitor quinapril and the AT1 receptor blocker losartan on arterial thrombus formation in the rat. Sprague-Dawley rats were fed regular chow or chow mixed with low-dose quinapril (0. 6 mg/kg/day), high-dose quinapril (1.2 mg/kg/day), or losartan (10 mg/kg/day) for 15 days. Abdominal aorta was exposed and wrapped with Whatman paper impregnated with 29% FeCl(3) (ferric chloride). Time to occlusive thrombus formation and weight of the thrombus were recorded. Aortic superoxide anion generation, platelet aggregation, plasma angiotensin II levels, and morphology of the thrombus were also examined. Both losartan and quinapril caused similar reductions in arterial pressure. Losartan did not affect the time to thrombus formation, whereas quinapril (both low and high doses) delayed the time to thrombus formation (P<.01 vs control). Weight of the thrombus was similar in all groups of rats. Platelet aggregation was inhibited by approximately 50 in both quinapril- and losartan-treated rats. The high-dose quinapril-treated rats showed markedly reduced vascular superoxide anion generation compared with the control rats (P<.05). Plasma angiotensin II levels were unaffected by quinapril treatment but were elevated 7-fold in losartan-treated rats (P <.001 vs. control rats). The thrombi in the control rats consisted of platelet aggregates, fibrin, and red blood cells. The intravascular platelet aggregates were much smaller in the quinapril-treated rats (P<.05 vs. control), but were similar in control and losartan-treated rats. In conclusion, quinapril but not losartan prolongs time to arterial thrombus formation and results in smaller platelet aggregates in the thrombus. Both quinapril and losartan decrease platelet aggregation, but only quinapril decreases superoxide anion generation. This effect on superoxide anion generation as well as mechanisms other than AT1 receptor blockade may underlie the salutary effect of quinapril on arterial thrombogenesis.

Angiotensin II↗
PubMed2000

Effect of stable fish oil on arterial thrombogenesis, platelet aggregation, and superoxide dismutase activity.

We examined the influence of dietary stable fish oil on aortic thrombosis, platelet aggregation, and superoxide dismutase (SOD) activity in a rat model. Twenty-nine Sprague-Dawley rats were fed regular chow supplemented with stable fish oil preparation (for 1 or 3 weeks), and 37 rats fed regular chow served as controls. The abdominal cavity was opened, and the abdominal aorta isolated. Whatman paper impregnated with 35% FeCl3 was wrapped around the surface of the aorta, and aortic flow was continuously recorded. In control rats, an occlusive platelet-fibrin-rich thrombus was formed in 21 +/- 3 min. Dietary fish oil in a time-dependent fashion delayed time to thrombus formation (24 +/- 2 min in rats fed fish oil for 1 week and 31 +/- 2 min in rats fed fish oil for 3 weeks), inhibited platelet aggregation (21 +/- 5% vs. 45 +/- 6%; p < 0.01) and increased SOD activity (p < 0.01). We conclude that dietary supplementation with stable fish oil delays formation of arterial thrombus, probably by reducing platelet aggregation and oxidative stress-associated arterial injury.

Animals↗
PubMed2000

Effects of alpha-tocopherol on ox-LDL-mediated degradation of IkappaB and apoptosis in cultured human coronary artery endothelial cells.

Experimental studies have demonstrated that vitamin E (alpha-tocopherol) may provide significant cytoprotection during cell injury. In this study, we examined the effects of alpha-tocopherol on oxidized low-density lipoprotein (ox-LDL)-induced apoptosis in human coronary artery endothelial cells (HCAECs). In addition, we examined the activation of NF-kappaB pathway in this process. Cultured HCAECs were treated with ox-LDL for 24 h. Incubation of HCAECs with ox-LDL resulted in apoptosis of HCAECs in a concentration-dependent manner, as determined by TUNEL and DNA laddering. Ox-LDL degraded IkappaB and activated NF-kappaB in HCAECs, as determined by Western blot analysis. Treatment with alpha-tocopherol (10 and 50 microM) decreased ox-LDL-mediated apoptosis as well as degradation of IkappaB and activation of NF-kappaB in HCAECs. High concentration of alpha-tocopherol (50 microM) was more effective than the low concentration of alpha-tocopherol (10 microM). Thus, ox-LDL induces apoptosis of HCAECs, in concurrence with degradation of IkappaB and activation of NF-kappaB. Alpha-tocopherol markedly decreases ox-LDL-induced effects.

Antioxidants↗
PubMed2000

Upregulation of endothelial receptor for oxidized LDL (LOX-1) by oxidized LDL and implications in apoptosis of human coronary artery endothelial cells: evidence from use of antisense LOX-1 mRNA and chemical inhibitors.

A specific lectin-like endothelial receptor for oxidized low density lipoprotein (LOX-1), distinct from the scavenger receptor in monocytes/macrophages, has been identified and cloned. In this study, we examined the regulation of LOX-1 by oxidized low density lipoprotein (ox-LDL) and determined the role of LOX-1 in ox-LDL-induced apoptosis of cultured human coronary artery endothelial cells (HCAECs). Incubation of HCAECs with ox-LDL (40 microg/mL), but not native LDL, for 24 hours markedly increased LOX-1 expression (mRNA and protein). After 48 hours of preincubation of HCAECs with a specific antisense to LOX-1 mRNA (antisense LOX-1), ox-LDL-mediated upregulation of LOX-1 was suppressed (P<0.01). In contrast, treatment of HCAECs with sense LOX-1 had no effect. Ox-LDL also induced apoptosis (determined by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling and DNA laddering) of HCAECs in a concentration- and time-dependent fashion. LOX-1 played an important role in ox-LDL-mediated apoptosis of HCAECs because antisense LOX-1 inhibited this effect of ox-LDL. Polyinosinic acid and carrageenan, 2 different chemical inhibitors of LOX-1, also decreased ox-LDL-mediated apoptosis of HCAECs. Nuclear factor (NF)-kappaB was markedly activated in ox-LDL-treated HCAECs. The critical role of NF-kappaB activation became evident in experiments with antisense LOX-1, which abolished ox-LDL-mediated NF-kappaB activation. In this process, an NF-kappaB inhibitor, caffeic acid phenethyl ester, also inhibited ox-LDL-mediated apoptosis of HCAECs. These findings indicate that ox-LDL upregulates its own endothelial receptor. Ox-LDL-induced apoptosis is mediated by the action of LOX-1. In this process, NF-kappaB activation may play an important role as a signal transduction mechanism.

Apoptosis↗
PubMed2000

Inflammation, infection and atherosclerosis: do antibacterials have a role in the therapy of coronary artery disease?

Since the recent publication of 3 studies on the use of antibacterials in patients with coronary artery disease (CAD), there has been a phenomenal interest in the role of infection in the genesis of CAD. It is now generally accepted that inflammation accompanies atherosclerosis from its initiation to the evolution of end-events. Inflammation may occur in response to traditional risk factors, such as hyperlipidaemia, smoking and diabetes mellitus. There is a recent resurgence of the concept that inflammation may have an infectious basis. This concept is based on the identification of microorganisms in the atherosclerotic plaque and seropositivity. The data on eradication of the offending organism with antibiotics and prevention of atherosclerosis-related events have, however, been inconsistent. This may reflect lack of precise understanding of steps leading to atherosclerosis and the evolution of acute ischaemic events. Further work in this area may help identify subsets of patient populations within which infection may play a causative role in the genesis of CAD. Targeted therapy then may be considered logical.

Anti-Bacterial Agents↗
PubMed2000

The potential role of antisense oligodeoxynucleotide therapy for cardiovascular disease.

Current drugs used in the treatment of cardiovascular disease are effective but compliance is poor and they are short acting (hours or one day). Gene therapy offers a way to produce long-lasting effects (weeks, months or years). Antisense inhibition is being developed for the treatment of hypertension, myocardial ischaemia and improved allograft survival in human vascular bypass grafts. We are currently using 2 strategies: (i) antisense oligodeoxynucleotides (AS-ODNs) which are delivered nonvirally and (ii) antisense DNA delivered in viral vectors to inhibit genes associated with vasoconstrictive properties. It is not necessary to know all the genes involved in hypertension, since many years of experience with drugs show which genes need to be controlled. AS-ODN are short, single-stranded DNA that can be injected in naked form or in liposomes. AS-ODN targeted to angiotensin type 1 (AT1) receptors, angiotensinogen (ATG), angiotensin converting enzyme (ACE) and beta1 adrenoceptors effectively reduce hypertension in rat models. A single dose is effective for up to one month when delivered with liposomes. No adverse or toxic effects have been detected, and repeated injections are effective. For viral delivery, adeno-associated virus (AAV) is used with a construct to include a cytomegalovirus or tissue-specific promoter, antisense DNA to ATG, ACE or AT1 receptors and a reporter gene. Results in rats and transgenic mice show significant prolonged reduction of hypertension, with a single dose administration of AAV-AS. Left ventricular hypertrophy is also reduced by antisense treatment. AS-ODNs to AT1 receptors, ATG and beta1 adrenoceptors provide cardioprotection from the effects of myocardial ischaemia. The AT1 receptor is more protective than losartan and does not increase plasma angiotensin as losartan does.

Animals↗
PubMed2000

Protection against myocardial dysfunction induced by global ischemia-reperfusion by antisense-oligodeoxynucleotides directed at beta(1)-adrenoceptor mRNA.

Plasma catecholamine levels rise, and myocardial beta(1)-adrenoceptor (beta(1)-AR) sensitivity increases during ischemia. These factors enhance myocardial injury and cardiac dysfunction. beta(1)-AR blockers are clinically used to protect heart against ischemia and to improve cardiac dysfunction in patients with ischemic heart disease, but these agents often cause intolerable side effects. To examine the potential cardioprotective effect of therapy with antisense-oligodeoxynucleotides directed at beta(1)-AR mRNA (beta(1)-AS-ODNs) during myocardial ischemia-reperfusion, Sprague-Dawley rats were treated with beta(1)-AS-ODNs or inverted-oligodeoxynucleotides (IN-ODNs), each 200 microg/rat. Hearts were excised, perfused, and subjected to global ischemia (30 min) followed by reperfusion (30 min). Other rats were given selective beta(1)-AR blocker atenolol (2 mg/kg) or saline before excising the hearts. Ischemia-reperfusion resulted in cardiac dysfunction, indicated by an increase in coronary perfusion pressure and left ventricular end-diastolic pressure and a decrease in developed left ventricular pressure, as well as evidence of lipid peroxidation in saline-treated rats (all P <.05 versus control values). Administration of AS-ODNs or atenolol, but not IN-ODNs, protected hearts against functional deterioration and lipid peroxidation (P <.05 versus saline or IN-ODNs treatment). AS-ODNs therapy appeared to be equivalent to atenolol in these effects. Expression of beta(1)-AR protein as well as mRNA in the myocardium were markedly up-regulated after ischemia-reperfusion, and treatment with beta(1)-AS-ODNs, but not atenolol, decreased the rise in enhanced expression of beta(1)-AR. These observations imply that beta(1)-AS-ODNs can ameliorate cardiac dysfunction after ischemia-reperfusion by reducing the expression of beta(1)-AR in the ischemic-reperfused myocardium.

Animals↗