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Articles by G Kaley
Total Records ( 2 ) for G Kaley
  I Rutkai , A Feher , N Erdei , D Henrion , Z Papp , I Edes , A Koller , G Kaley and Z. Bagi
  Aims

Type 2 diabetes mellitus is frequently associated with hypertension, but the underlying mechanisms are not completely understood. We tested the hypothesis that activation of type 1 prostaglandin E2 (PGE2) receptor (EP1) increases skeletal muscle arteriolar tone and blood pressure in mice with type 2 diabetes.

Methods and results

In 12-week-old, male db/db mice (with homozygote mutation in leptin receptor), systolic blood pressure was significantly elevated, compared with control heterozygotes. Isolated, pressurized gracilis muscle arterioles (~90 µm) of db/db mice exhibited an enhanced pressure- and angiotensin II (0.1–10 nM)-induced tone, which was reduced by the selective EP1 receptor antagonist, AH6809 (10 µM), to the level observed in arterioles of control mice. Exogenous application of PGE2 (10 pM–100 nM) or the selective agonist of the EP1 receptor, 17-phenyl-trinor-PGE2 (10 pM–100 nM), elicited arteriolar constrictions that were significantly enhanced in db/db mice (max: 31 ± 4 and 29 ± 5%), compared with controls (max: 20 ± 2 and 14 ± 3%, respectively). In the aorta of db/db mice, an increased protein expression of EP1, but not EP4, receptor was also detected by western immunoblotting. Moreover, we found that oral administration of the EP1 receptor antagonist, AH6809 (10 mg/kg/day, for 4 days), significantly reduced the systolic blood pressure in db/db, but not in control mice.

Conclusion

Activation of EP1 receptors increases arteriolar tone, which could contribute to the development of hypertension in the db/db mice.

  N Suematsu , C Ojaimi , F. A Recchia , Z Wang , Y Skayian , X Xu , S Zhang , P. M Kaminski , D Sun , M. S Wolin , G Kaley and T. H. Hintze
 

Rationale: Patients on a low salt (LS) diet have increased mortality.

Objective: To determine whether reduction in NO bioactivity may contribute to the LS-induced cardiac dysfunction and mortality.

Methods and Results: Adult male mongrel dogs were placed on LS (0.05% sodium chloride) for 2 weeks. Body weight (25.4±0.4 to 23.6±0.4 kg), left ventricular systolic pressure (137.0±3.4 to 124.0±6.7 mm Hg), and mean aortic pressure (111±3.1 to 98±4.3 mm Hg) decreased. Plasma angiotensin II concentration increased (4.4±0.7 to 14.8±3.7 pg/mL). Veratrine-induced (5 µg/kg) NO-mediated vasodilation was inhibited by 44% in LS; however, the simultaneous intravenous infusion of ascorbic acid or apocynin acutely and completely reversed this inhibition. In LS heart tissues, lucigenin chemiluminescence was increased 2.3-fold to angiotensin II (10–8 mol/L), and bradykinin (10–4 mol/L) induced reduction of myocardial oxygen consumption in vitro was decreased (40±1.3% to 16±6.3%) and completely restored by coincubation with tiron, tempol or apocynin. Switching of substrate uptake from free fatty acid to glucose by the heart was observed (free fatty acid: 8.97±1.39 to 4.53±1.12 µmol/min; glucose: 1.31±0.52 to 6.86±1.78 µmol/min). Western blotting indicated an increase in both p47phox (121%) and gp91phox (44%) as did RNA microarray analysis (433 genes changed) showed an increase in p47phox (1.6-fold) and gp91phox (2.0 fold) in the LS heart tissue.

Conclusions: LS diet induces the activation of the renin–angiotensin system, which increases oxidative stress via the NADPH oxidase and attenuates NO bioavailability in the heart.

 
 
 
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