الفهرس 
IntroductionOnly 14 pages are availabe for public view
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Abstract
Diabetes predisposes to deleterious cardiovascular outcomes including hypertension and baroreflex dysfunction. The mechanisms of diabetes-induced cardiovascular complications include endothelial dysfunction, oxidative stress, inflammation and sympathoexcitation. Pharmacologic interventions that reduce oxidative stress and sympathetic activity are believed to confer cardiovascular protection. Relying on this aspect, a sympatholytic imidazoline-1 receptor (I1R) agonist (moxonidine), which also believed to have antioxidant properties, was used in the current study.
Less attention was given to the potential beneficial cardiovascular and glycemic effects of endogenous gaseous cellular modulator, H2S. However, the blunted cystathionine-γ lyase enzyme (CSE) activity, H2S-synthesizing enzyme, implicated in hypertension and myocardial dysfunction associated with diabetes brought an interest in investigating this pathway. Herein, the hypothesis that CSE-derived H2S mediates the cardiovascular protection conferred by I1R agonist, moxonidine, in diabetic rat model was tested. Such hypothesis originated from the existence of common signaling cascades triggered by I1R activation and H2S gas.
In the current study, streptozotocin “STZ”, was utilized to induce diabetes in male Wistar rats. Four weeks later, STZ-treated rats received vehicle, moxonidine, H2S donor (NaHS) or CSE-inhibitor, DL-propargylglycine, (PPG) for successive three weeks. NaHS or PPG was also combined with the higher dose of moxonidine (Mox6). In similar manner, citrate buffer-treated rats (vehicle for STZ) received vehicle, NaHS or PPG in the assigned doses and served as nondiabetic (ND) controls.Diabetes predisposes to deleterious cardiovascular outcomes including hypertension and baroreflex dysfunction. The mechanisms of diabetes-induced cardiovascular complications include endothelial dysfunction, oxidative stress, inflammation and sympathoexcitation. Pharmacologic interventions that reduce oxidative stress and sympathetic activity are believed to confer cardiovascular protection. Relying on this aspect, a sympatholytic imidazoline-1 receptor (I1R) agonist (moxonidine), which also believed to have antioxidant properties, was used in the current study.
Less attention was given to the potential beneficial cardiovascular and glycemic effects of endogenous gaseous cellular modulator, H2S. However, the blunted cystathionine-γ lyase enzyme (CSE) activity, H2S-synthesizing enzyme, implicated in hypertension and myocardial dysfunction associated with diabetes brought an interest in investigating this pathway. Herein, the hypothesis that CSE-derived H2S mediates the cardiovascular protection conferred by I1R agonist, moxonidine, in diabetic rat model was tested. Such hypothesis originated from the existence of common signaling cascades triggered by I1R activation and H2S gas.
In the current study, streptozotocin “STZ”, was utilized to induce diabetes in male Wistar rats. Four weeks later, STZ-treated rats received vehicle, moxonidine, H2S donor (NaHS) or CSE-inhibitor, DL-propargylglycine, (PPG) for successive three weeks. NaHS or PPG was also combined with the higher dose of moxonidine (Mox6). In similar manner, citrate buffer-treated rats (vehicle for STZ) received vehicle, NaHS or PPG in the assigned doses and served as nondiabetic (ND) controls.Diabetes predisposes to deleterious cardiovascular outcomes including hypertension and baroreflex dysfunction. The mechanisms of diabetes-induced cardiovascular complications include endothelial dysfunction, oxidative stress, inflammation and sympathoexcitation. Pharmacologic interventions that reduce oxidative stress and sympathetic activity are believed to confer cardiovascular protection. Relying on this aspect, a sympatholytic imidazoline-1 receptor (I1R) agonist (moxonidine), which also believed to have antioxidant properties, was used in the current study.
Less attention was given to the potential beneficial cardiovascular and glycemic effects of endogenous gaseous cellular modulator, H2S. However, the blunted cystathionine-γ lyase enzyme (CSE) activity, H2S-synthesizing enzyme, implicated in hypertension and myocardial dysfunction associated with diabetes brought an interest in investigating this pathway. Herein, the hypothesis that CSE-derived H2S mediates the cardiovascular protection conferred by I1R agonist, moxonidine, in diabetic rat model was tested. Such hypothesis originated from the existence of common signaling cascades triggered by I1R activation and H2S gas.
In the current study, streptozotocin “STZ”, was utilized to induce diabetes in male Wistar rats. Four weeks later, STZ-treated rats received vehicle, moxonidine, H2S donor (NaHS) or CSE-inhibitor, DL-propargylglycine, (PPG) for successive three weeks. NaHS or PPG was also combined with the higher dose of moxonidine (Mox6). In similar manner, citrate buffer-treated rats (vehicle for STZ) received vehicle, NaHS or PPG in the assigned doses and served as nondiabetic (ND) controls.