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Biomedical subjects

P Mehta

Publications and source records attributed to P Mehta.

At least 55 records · Page 3Linked to original sources
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↗
PubMed1999

A novel glycosulfopeptide binds to P-selectin and inhibits leukocyte adhesion to P-selectin.

P-selectin glycoprotein ligand-1 (PSGL-1) is a dimeric membrane mucin on leukocytes that binds selectins. The molecular features of PSGL-1 that determine this high affinity binding are unclear. Here we demonstrate the in vitro synthesis of a novel glycosulfopeptide (GSP-6) modeled after the extreme N terminus of PSGL-1, which has been predicted to be important for P-selectin binding. GSP-6 contains three tyrosine sulfate (TyrSO(3)) residues and a monosialylated, core 2-based O-glycan with a sialyl Lewis x (C2-O-sLe(x)) motif at a specific Thr residue. GSP-6 binds tightly to immobilized P-selectin, whereas glycopeptides lacking either TyrSO(3) or C2-O-sLe(x) do not detectably bind. Remarkably, an isomeric glycosulfopeptide to GSP-6, termed GSP-6', which contains sLe(x) on an extended core 1-based O-glycan, does not bind immobilized P-selectin. Equilibrium gel filtration analysis revealed that GSP-6 binds to soluble P-selectin with a K(d) of approximately 350 nM. GSP-6 (<5 microM) substantially inhibits neutrophil adhesion to P-selectin in vitro, whereas free sLe(x) (5 mM) only slightly inhibits adhesion. In contrast to the inherent heterogeneity of post-translational modifications of recombinant proteins, glycosulfopeptides permit the placement of sulfate groups and glycans of precise structure at defined positions on a polypeptide. This approach should expedite the probing of structure-function relationships in sulfated and glycosylated proteins, and may facilitate development of novel drugs to treat inflammatory diseases involving P-selectin-mediated leukocyte adhesion.

Amino Acid Sequence↗
PubMed1999

Human brain short chain L-3-hydroxyacyl coenzyme A dehydrogenase is a single-domain multifunctional enzyme. Characterization of a novel 17beta-hydroxysteroid dehydrogenase.

Human brain short chain L-3-hydroxyacyl-CoA dehydrogenase (SCHAD) was found to catalyze the oxidation of 17beta-estradiol and dihydroandrosterone as well as alcohols. Mitochondria have been demonstrated to be the proper location of this NAD+-dependent dehydrogenase in cells, although its primary structure is identical to an amyloid beta-peptide binding protein reportedly associated with the endoplasmic reticulum (ERAB). This fatty acid beta-oxidation enzyme was identified as a novel 17beta-hydroxysteroid dehydrogenase responsible for the inactivation of sex steroid hormones. The catalytic rate constant of the purified enzyme was estimated to be 0.66 min-1 with apparent Km values of 43 and 50 microM for 17beta-estradiol and NAD+, respectively. The catalytic efficiency of this enzyme for the oxidation of 17beta-estradiol was comparable with that of peroxisomal 17beta-hydroxysteroid dehydrogenase type 4. As a result, the human SCHAD gene product, a single-domain multifunctional enzyme, appears to function in two different pathways of lipid metabolism. Because the catalytic functions of human brain short chain L-3-hydroxyacyl-CoA dehydrogenase could weaken the protective effects of estrogen and generate aldehydes in neurons, it is proposed that a high concentration of this enzyme in brain is a potential risk factor for Alzheimer's disease.

17-Hydroxysteroid Dehydrogenases↗
PubMed1999

Modulation of constitutive nitric oxide synthase, bcl-2 and Fas expression in cultured human coronary endothelial cells exposed to anoxia-reoxygenation and angiotensin II: role of AT1 receptor activation.

BACKGROUND: Angiotensin II (Ang II) plays a critical role in the pathophysiology of myocardial ischemia-reperfusion injury. We have recently shown that reoxygenation following a period of anoxia causes apoptosis of cultured human coronary artery endothelial cells (HCAECs). Ang II further enhances apoptosis of HCAECs via Ang II type 1 receptor (AT1R) activation. Recent studies suggest an important role of constitutive nitric oxide synthase (cNOS), Fas and bcl-2 proteins in apoptosis. This study was designed to examine the modulation of cNOS, and Fas and bcl-2 expression in HCAECs during exposure to anoxia-reoxygenation and Ang II. METHODS AND RESULTS: HCAECs were exposed to anoxia-reoxygenation and Ang II. Anoxia-reoxygenation significantly decreased cNOS mRNA, protein and activity in cultured HCAECs (P < 0.05 vs. control). Anoxia-reoxygenation also caused an increase in Fas and a decrease in bcl-2 protein expression in cultured HCAECs (both P < 0.05 vs. control). The presence of Ang II (0.3 microM) further enhanced these effects of anoxia-reoxygenation on cNOS, Fas and bcl-2 expression. The effects of Ang II were significantly attenuated by the AT1R inhibitor losartan (10 microM). CONCLUSION: During exposure of HCAECs to anoxia-reoxygenation and Ang II, AT1R activation induces important changes in cNOS mRNA, protein expression and activity, as well as bcl-2 and Fas protein expression which may have a bearing on the development of apoptosis.

Analysis of Variance↗
PubMed1999

Potentiating effects of hyper-osmolality and epidermal growth factor on the release of arachidonic acid in human glomerular mesangial cells.

Studies were performed to determine the interactive effects of high concentrations of glucose (HG) and epidermal growth factor (EGF) on the release of arachidonic acid (3H-AA) in human glomerular mesangial cells (MC) in culture. Since high glucose has been reported to increase the mass of diacylglycerol (DAG) in MC, the HG-induced release of 3H-AA was compared to that initiated by the phorbol ester, PMA. It was found that when media contained high levels (25 mM) of glucose, the release of 3H-AA was increased significantly by 8.4% (change from control) after 1 h of exposure and was maintained at values not significantly different from this level for the next 2 h. After 3-h exposure, there was no significant difference between 25 and 50 mM glucose, suggesting that the effects of glucose are saturating at 25 mM. After 1-h exposure, 3H-AA release was also increased by PMA; however, the increase was larger and the peak increase was delayed until after 1 h. 3H-AA release was significantly increased by epidermal growth factor (EGF) by 8.5% after 1 h and was maintained at this level after 2 and 3 h of exposure. In the presence of HG, EGF increased 3H-AA release by 24.6% after the 1st hour and by 20.4 and 19.4%, after the 2nd and 3rd hours, respectively. Mannitol (20 mM), added as an osmotic control, increased 3H-AA release by 6.2% and also significantly enhanced the effects of EGF after 3 h. The experimental values (19.0%) for the release of 3H-AA after 3-h exposure to EGF in combination with either high glucose or mannitol were significantly greater than the expected (added) values (12.1%). These results demonstrate that as a result of an elevated solution osmolality, high glucose acts synergistically with EGF to increase the release of 3H-AA in human mesangial cells.

Arachidonic Acid↗
PubMed1999

Presenilin-1 forms complexes with the cadherin/catenin cell-cell adhesion system and is recruited to intercellular and synaptic contacts.

In MDCK cells, presenilin-1 (PS1) accumulates at intercellular contacts where it colocalizes with components of the cadherin-based adherens junctions. PS1 fragments form complexes with E-cadherin, beta-catenin, and alpha-catenin, all components of adherens junctions. In confluent MDCK cells, PS1 forms complexes with cell surface E-cadherin; disruption of Ca(2+)-dependent cell-cell contacts reduces surface PS1 and the levels of PS1-E-cadherin complexes. PS1 overexpression in human kidney cells enhances cell-cell adhesion. Together, these data show that PS1 incorporates into the cadherin/catenin adhesion system and regulates cell-cell adhesion. PS1 concentrates at intercellular contacts in epithelial tissue; in brain, it forms complexes with both E- and N-cadherin and concentrates at synaptic adhesions. That PS1 is a constituent of the cadherin/catenin complex makes that complex a potential target for PS1 FAD mutations.

Animals↗
PubMed1999

Increased clearance of tacrolimus in children: need for higher doses and earlier initiation prior to bone marrow transplantation.

The pharmacokinetics of tacrolimus have been studied in healthy volunteers and in adults undergoing bone marrow transplantation. However, there is little information on the pharmacokinetics of tacrolimus in children undergoing BMT. We studied pharmacokinetics of tacrolimus in seven patients (age 8-17 years) undergoing allogeneic stem cell transplantation. Four patients received matched unrelated donor (MUD) transplants, two underwent HLA-matched related donor transplants, and one underwent an umbilical cord blood donor transplant. All patients received tacrolimus by continuous infusion at 0.03-0.04 mg/kg/day beginning on the day prior to transplant. Tacrolimus whole blood concentrations were monitored by microparticle enzyme immunoassay. Our goal was to maintain a blood tacrolimus level of 10-20 microg/ml. Once patients were tolerating oral medications, tacrolimus infusion was converted to oral dosing using a 4:1 conversion. Dose of tacrolimus and resulting tacrolimus concentrations were recorded and the total body clearance of tacrolimus was calculated retrospectively. The mean clearance, based on first steady-state tacrolimus concentrations necessary for achieving a therapeutic level (10-20 microg/ml), was 108.1 ml/h/kg (range 79.7-142.0 ml/h/kg), greater than that reported in adult BMT patients (71 +/- 34 ml/h/kg). The average dose required to achieve that therapeutic range was 0.0354 mg/kg/day as an intravenous continuous infusion. Over the entire course of intravenous tacrolimus, mean clearance was 97.0 ml/h/kg (range 33.4-153.3 ml/h/kg). In six of the seven patients, clearance values dropped after 2-4 weeks of therapy by an average of 32.5 ml/h/kg. In two patients, sharp drops in clearance were temporally related to changes in liver function tests. Three of the seven patients died of severe acute GVHD; all these had undergone matched unrelated donor transplantation, and two of these three had initial clearance levels over 120 ml/h/kg. Thus, children appear to have more rapid tacrolimus clearance than adults and may need to begin therapy earlier in order to obtain stable and optimal levels. More studies are needed to confirm these preliminary results.

Adolescent↗
PubMed1999

Distinct secretases, a cysteine protease and a serine protease, generate the C termini of amyloid beta-proteins Abeta1-40 and Abeta1-42, respectively.

The carboxy-terminal ends of the 40- and 42-amino acids amyloid beta-protein (Abeta) may be generated by the action of at least two different proteases termed gamma(40)- and gamma(42)-secretase, respectively. To examine the cleavage specificity of the two proteases, we treated amyloid precursor protein (APP)-transfected cell cultures with several dipeptidyl aldehydes including N-benzyloxycarbonyl-Leu-leucinal (Z-LL-CHO) and the newly synthesized N-benzyloxycarbonyl-Val-leucinal (Z-VL-CHO). All dipeptidyl aldehydes tested inhibited production of both Abeta1-40 and Abeta1-42. Changes in the P1 and P2 residues of these aldehydes, however, indicated that the amino acids occupying these positions are important for the efficient inhibition of gamma-secretases. Peptidyl aldehydes inhibit both cysteine and serine proteases, suggesting that the two gamma-secretases belong to one of these mechanistic classes. To differentiate between the two classes of proteases, we treated our cultures with the specific cysteine protease inhibitor E-64d. This agent inhibited production of secreted Abeta1-40, with a concomitant accumulation of its cellular precursor indicating that gamma(40)-secretase is a cysteine protease. In contrast, this treatment increased production of secreted Abeta1-42. No inhibition of Abeta production was observed with the potent calpain inhibitor I (acetyl-Leu-Leu-norleucinal), suggesting that calpain is not involved. Together, these results indicate that gamma(40)-secretase is a cysteine protease distinct from calpain, whereas gamma(42)-secretase may be a serine protease. In addition, the two secretases may compete for the same substrate. Dipeptidyl aldehyde treatment of cultures transfected with APP carrying the Swedish mutation resulted in the accumulation of the beta-secretase C-terminal APP fragment and a decrease of the alpha-secretase C-terminal APP fragment, indicating that this mutation shifts APP cleavage from the alpha-secretase site to the beta-secretase site.

Aldehydes↗
PubMed1999

Nitric oxide successfully used to treat acute chest syndrome of sickle cell disease in a young adolescent.

OBJECTIVES: To report a case of acute chest syndrome (ACS) of sickle cell disease treated successfully with nitric oxide and to review the physiologic effects of nitric oxide and its potential ability to improve outcome in ACS. DESIGN: Descriptive case report. SETTING: Eighteen-bed pediatric intensive care unit in a university children's hospital. PATIENT: A 15-yr-old black male with sickle cell disease, bilateral pulmonary infiltrates, refractory hypoxemia, and unstable hemodynamics. INTERVENTION: In addition to exchange transfusion, invasive hemodynamic monitoring, and aggressive ventilatory support, inhaled nitric oxide was administered in the gas mixture in a concentration of 20 ppm for 72 hrs. MEASUREMENTS AND MAIN RESULTS: Cardiac output, pulmonary arterial pressure, pulmonary artery occlusion pressure, systemic vascular resistance, pulmonary vascular resistance, shunt fraction, and alveolar-arterial oxygen gradient were compared with and without inhaled nitric oxide. Marked reductions in pulmonary arterial pressure and pulmonary vascular resistance were noted. Cardiac output improved, and shunt fraction and alveolar-arterial oxygen gradient were markedly reduced. The patient required decreased ventilator and hemodynamic support and rapidly made a complete recovery. CONCLUSIONS: Nitric oxide may be beneficial for patients with ACS because of its ability to ameliorate pulmonary hypertension and ventilation/perfusion mismatch. Nitric oxide may confer some protection against polymerization of sickle hemoglobin and exert a reversible antiplatelet effect that may be beneficial in ACS. Further study is necessary to determine the safety and efficacy of inhaled nitric oxide as a treatment for ACS.

Acute Disease↗
PubMed1999

In rat tIMCD, NH4+ uptake by Na+-K+-ATPase is critical to net acid secretion during chronic hypokalemia.

The purpose of this study was to determine the magnitude of Na+ pump-mediated NH4+ uptake in the terminal inner medullary collecting duct (tIMCD) at K+ and NH4+ concentrations observed in vivo in the inner medullary interstitium of normal and in K+-restricted rats. Interstitial K+ and NH4+ concentrations in the terminal half of the inner medulla were taken to be 10 and 6 mM in K+-restricted rats, but 30 and 6 mM in K+-replete rats. In tubules from K+-restricted rats, when perfused at a K+ concentration of 10 mM, addition of ouabain to the bath reduced total bicarbonate flux (JtCO2) by 40% and increased intracellular pH (pHi), indicating significant NH4+ uptake by the Na+-K+-ATPase. In tubules from K+-restricted rats, JtCO2 was reduced with increased extracellular K+. At a K+ concentration of 30 mM, ouabain addition neither reduced JtCO2 nor increased pHi in tubules from rats of either treatment group. In conclusion, in the tIMCD from hypokalemic rats, 1) acute changes in extracellular K+ concentration modulate net acid secretion, and 2) Na+ pump-mediated NH4+ uptake should be an important pathway mediating transepithelial net acid secretion in vivo.

Ammonia↗
PubMed1999

Thalidomide in children undergoing bone marrow transplantation: series at a single institution and review of the literature.

Thalidomide has one of the most notorious drug histories because of its teratogenicity. Its widespread use in the 1960s led to a worldwide epidemic of phocomelia in inborns; this in turn led to its complete ban in most of the world. However, it has now been licensed for selected indications including graft-versus-host-disease (GVHD) after bone marrow transplantation, wasting associated with tuberculosis and human immunodeficiency virus infection, and leprosy. Little is known, however, about its use in children in these settings. Therefore, we report our experience and review the literature on thalidomide in children for GVHD after bone marrow transplantation. We studied 6 patients, 2 with chronic GVHD, 2 with acute GVHD, and 2 with acute GVHD progressing into chronic disease. One patient with chronic GVHD had a complete response, whereas the other had a partial response. Side effects consisted primarily of sedation and constipation, which are reported previously and well known side effects. None had neuropathy. One patient had rash, eosinophilia, and early pancreatitis that began shortly after initiation of thalidomide, persisted, and resolved only after discontinuation of thalidomide. Eosinophilia and pancreatitis are both previously unreported side effects or associated findings of thalidomide treatment. Review of the literature reveals three major studies of thalidomide in GVHD; of these two included children and adults together, and one in which age range of patients was not mentioned. In addition, four series of children receiving only thalidomide are reported. These series contained 1 to 14 patients each. Results show efficacy in at least 50% of children with chronic GVHD and little or no efficacy in children with exclusively acute GVHD. Side effects are similar to those reported in adults and consisted mostly of sedation and constipation, both of which subsided over time and resolved after discontinuing the drug. We speculate on the reasons for which thalidomide is more effective in chronic, compared with acute, GVHD in children, and make recommendations for future study.

Acute Disease↗
PubMed1999

Role of TGF-beta1 in platelet-mediated cardioprotection during ischemia-reperfusion in isolated rat hearts.

Platelets protect myocardium against ischemia-reperfusion injury. This study examined the role of platelet-derived TGF-beta1 in cardioprotection during ischemia-reperfusion. Isolated Sprague Dawley rat hearts were perfused with K-H buffer and subjected to 25 min of global ischemia followed by 30 min of reperfusion. Ischemia-reperfusion resulted in myocardial dysfunction indicated by increase in CPP and LVEDP, and decrease in dLVP. Perfusion of hearts with washed platelets or supernatant of aggregated platelets attenuated (P < 0.01) of myocardial dysfunction following ischemia-reperfusion. Ischemia-reperfusion resulted in a decrease in myocardial TGF-beta1 determined by immunohistochemistry. ELISA showed an increase in latent TGF-beta1, but a decrease in active TGF-beta1. Perfusion of hearts with platelets or aggregated platelet supernatant preserved myocardial TGF-beta1 content upon ischemia-reperfusion. Perfusion of hearts with recombinant TGF-beta1 also resulted in cardioprotection following ischemia-reperfusion qualitatively similar to that observed with platelets or aggregated platelet supernatants. RT-PCR analysis showed an increase in myocardial TGF-beta1 mRNA following ischemia-reperfusion. These observations indicate that platelets protect the myocardium against ischemia-reperfusion-mediated dysfunction at least in part by releasing TGF-beta1. Increase in both TGF-beta1 mRNA and latent TGF-beta1 does not indicate a defect in the translation of mRNA. Reduction in myocardial TGF-beta1 following ischemia-reperfusion suggests a defect in the conversion of latent TGF-beta1 to active TGF-beta1.

Animals↗
PubMed1999

Quantification of sub-femtomole amounts of Alzheimer amyloid beta peptides.

We evaluated methods for the quantitative Western blot analysis of A beta 1-40 and A beta 1-42. Both chromogenic and chemiluminescent detection methods gave similar sensitivities (0.15 fmol of A beta 1-40 and 0.3 fmol of A beta 1-42); however, the chromogenic method was more rapid, simpler, less expensive and gave fewer background problems; consequently, it yielded more reliable results. Adsorption to various types of laboratory plasticware can greatly interfere with the accurate measurement of A beta, but this can be prevented by the addition of SDS or bovine serum albumin. Among several methods for concentrating A beta from biological materials, immunoadsorption to Sepharose-bound antibodies was the most efficient. It yielded 50% recovery of 1 pM A beta 1-42 or A beta 1-40 and so was a suitable method to measure A beta levels in human plasma. Through combined immunoadsorption and Western blotting we could determine the amounts of A beta isoforms secreted from 1 x 10(6) cells after a culture period as short as 1 h. This eliminates the need to use radiolabelling or over-expression to study A beta precursor processing Bovine serum contains subnanomolar A beta levels, similar to those that reportedly stimulate cell proliferation. That cultured cells quickly secrete these levels of A beta suggests that the peptide might exert an autocrine effect.

Alzheimer Disease↗
PubMed1998

Affinity and kinetic analysis of P-selectin binding to P-selectin glycoprotein ligand-1.

Leukocytes use the cell-surface mucin P-selectin glycoprotein ligand-1 (PSGL-1) to tether to and roll on P-selectin on activated endothelial cells and platelets. By using surface plasmon resonance, we measured the affinity and kinetics of binding of soluble monomeric human P-selectin to immobilized PSGL-1 from human neutrophils. Binding was specific, as documented by its Ca2+-dependence, its inhibition by specific monoclonal antibodies to P-selectin and PSGL-1, and its abrogation by treating PSGL-1 with sialidase. Similar binding was observed for soluble P-selectin that contained the lectin and epidermal growth factor domains plus all nine consensus repeats, and for a soluble construct that contained only the lectin and epidermal growth factor domains. Soluble P-selectin bound saturably to a single class of sites on PSGL-1 with a dissociation constant (Kd) of 320 +/- 20 nM. The measured koff was 1.4 +/- 0.1 s-1, and the calculated kon was 4.4 x 10(6) M-1 s-1. We conclude that monomeric P-selectin binds to PSGL-1 with fast association and dissociation rates and relatively high affinity. These features may be important for efficient tethering and rolling of leukocytes at physiologic densities of PSGL-1 and P-selectin.

Animals↗
PubMed1998

Critical role of AT1 receptor expression after ischemia/reperfusion in isolated rat hearts: beneficial effect of antisense oligodeoxynucleotides directed at AT1 receptor mRNA.

To examine the relevance of angiotensin II type 1 receptor (AT1R) expression in the determination of myocardial function after ischemia/reperfusion, Sprague-Dawley rats were treated intravenously with antisense oligodeoxynucleotides (AS-ODNs) directed at AT1R mRNA (100 microg/rat, n=9) or scrambled antisense oligodeoxynucleotides (Scr-ODNs, 100 microg/rat, n=6). Both AS-ODNs and Scr-ODNs were given along with 300 microg/rat of liposome DOTAP/DOPE, a positive electron carrier (wt:wt= 1:1). The hearts from AS-ODN- or Scr-ODN-treated rats were excised 24 hours later, perfused in vitro, and subjected to 25 minutes of global ischemia followed by 30 minutes of reperfusion. Parallel groups of rats were given the specific AT1R antagonist losartan (10 mg/kg IV, n=6) or saline (n=7) 4 to 6 hours before excising the hearts. Ischemia/reperfusion resulted in a significant increase in myocardial AT1R expression (autoradiography and binding assay) and myocardial dysfunction, indicated by increases in coronary perfusion pressure and left ventricular end-diastolic pressure and a decrease in developed left ventricular pressure (all P<0.01 versus baseline) in the saline-treated group. AT1R protein and mRNA levels also increased in ischemic/ reperfused myocardial tissues. Administration of AS-ODNs or losartan, but not Scr-ODNs, preserved myocardial function and blocked the increased AT1R binding after ischemia/reperfusion (both P<0.01). Myocardial AT1R mRNA levels were not affected by either AS-ODNs or losartan, and the AT1R protein levels were significantly reduced by AS-ODN, but not losartan, treatment. Plasma angiotensin II levels increased after administration of losartan but not after administration of AS-ODNs. These observations imply a critical role of AT1R upregulation in determining myocardial function immediately after ischemia/reperfusion. AS-ODNs to AT1R mRNA may be more beneficial than losartan, because losartan does not affect the plasma angiotensin II level. The sustained increase in AT1R mRNA, but diminished protein expression, in rat hearts treated with AS-ODNs suggests that AS-ODNs block AT1R at the translational level.

Analysis of Variance↗