Effect of diabetes on aortic nitric oxide synthesis in spontaneously hypertensive rats; does captopril modulate this effect?

Ibrahim, Mohamed; Kanzaki, Tetsuto; Yamagata, S; Satoh, Nobunori; Ueda, Shiro

doi:10.1016/j.lfs.2005.02.010

Cited by 8 publications

(2 citation statements)

References 47 publications

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“…The latter might also result from reduced NO synthesis, caused by persistent hyperglycemia, reported here (Fig. 5B) and in reported studies (Ibrahim et al, 2005; Pieper, 1998). By the same token, the enhanced peripheral and central NO generation (Mukaddam-Daher et al, 2009), the central sympathoinhibition (Ernsberger et al, 1999; Honda et al, 2013; Li and Abdel-Rahman, 2007) as well as the improvement of baroreflex function here (Table 2), and in reported studies (Turcani, 2008), might contribute to moxonidine-evoked hypotension in STZ rats.…”

Section: Discussionsupporting

confidence: 77%

Cystathionine-γ lyase-derived hydrogen sulfide mediates the cardiovascular protective effects of moxonidine in diabetic rats

El-Sayed

Zakaria

Abdel-Ghany

et al. 2016

European Journal of Pharmacology

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Blunted cystathionine-γ lyase (CSE) activity (reduced endogenous H2S-level) is implicated in hypertension and myocardial dysfunction in diabetes. Here, we tested the hypothesis that CSE derived H2S mediates the cardiovascular protection conferred by the imidazoline I1 receptor agonist moxonidine in a diabetic rat model. We utilized streptozotocin (STZ; 55 mg/kg i.p) to induce diabetes in male Wistar rats. Four weeks later, STZ-treated rats received vehicle, moxonidine (2 or 6 mg/kg; gavage), CSE inhibitor DL-propargylglycine, (37.5 mg/kg i.p) or DL-propargylglycine with moxonidine (6 mg/kg) for 3 weeks. Moxonidine improved the glycemic state, and reversed myocardial hypertrophy, hypertension and baroreflex dysfunction in STZ-treated rats. Ex vivo studies revealed that STZ caused reductions in CSE expression/activity, H2S and nitric oxide (NO) levels and serum adiponectin and elevations in myocardial imidazoline I1 receptor expression, p38 and extracellular signal-regulated kinase, ERK1/2, phosphorylation and lipid peroxidation (expressed as malondialdehyde). Moxonidine reversed these biochemical responses, and suppressed the expression of death associated protein kinase-3. Finally, pharmacologic CSE inhibition (DL-propargylglycine) abrogated the favorable cardiovascular, glycemic and biochemical responses elicited by moxonidine. These findings present the first evidence for a mechanistic role for CSE derived H2S in the glycemic control and in the favorable cardiovascular effects conferred by imidazoline I1 receptor activation (moxonidine) in a diabetic rat model.

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Section: Discussionsupporting

confidence: 77%

Cystathionine-γ lyase-derived hydrogen sulfide mediates the cardiovascular protective effects of moxonidine in diabetic rats

El-Sayed

Zakaria

Abdel-Ghany

et al. 2016

European Journal of Pharmacology

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“…The IUPD rat was diabetic and therefore more complicated than spontaneously hypertensive (SH) rat [25]. It was reported that Capto prevented impaired endothelial response to acetylcholine in SH rats, while antihypertensive treatment did not restore endothelial function in rats with hypertension and diabetes [26-28]. We have also recently shown that restoration of endothelial response to acetylcholine in Zucker diabetic fatty rats required activation of peroxisome proliferation-activated receptor γ, thereby suggesting that this part of endothelial function in diabetic rats is regulated in an angiotensin-independent manner [29].…”

Section: Discussionmentioning

confidence: 99%

Protein Kinase C inhibition ameliorates functional endothelial insulin resistance and Vascular Smooth Muscle Cell hypersensitivity to insulin in diabetic hypertensive rats

Bean

Kassab

et al. 2011

Cardiovasc Diabetol

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ObjectiveInsulin resistance, diabetes, and hypertension are considered elements of metabolic syndrome which is associated with vascular dysfunction. We investigated whether inhibition of protein kinase C (PKC) would affect vascular function in diabetic hypertensive (DH) rats.MethodsA combination of type 2 diabetes and arterial hypertension was produced in male Sprague Dawley rats by intrauterine protein deprivation (IUPD) followed by high salt diet. At the age of 32 weeks, DH rats were treated for 2 weeks with the angiotensin-converting enzyme inhibitor captopril (Capto, 30 mg/kg), PKC inhibitor ruboxistaurin (RBX, 50 mg/kg) or vehicle (n = 8 per group) and blood pressure was monitored using telemetry. At the end of experiments, femoral arteries were dissected, and vascular reactivity was evaluated with isovolumic myography.ResultsThe IUPD followed by high salt diet resulted in significant elevation of plasma glucose, plasma insulin, and blood pressure. Endothelium-dependent vascular relaxation in response to acetylcholine was blunted while vascular contraction in response to phenylephrine was enhanced in the DH rats. Neither Capto nor RBX restored endothelium-dependent vascular relaxation while both suppressed vascular contraction. Ex-vivo incubation of femoral arteries from control rats with insulin induced dose-response vasorelaxation while insulin failed to induce vasorelaxation in the DH rat arteries. In the control arteries treated with endothelial nitric oxide synthase inhibitor L-NAME, insulin induced vasoconstriction that was exacerbated in DH rats. Capto and RBX partially inhibited insulin-stimulated vascular contraction.ConclusionThese findings suggest that PKC inhibition ameliorates functional endothelial insulin resistance and smooth muscle cell hypersensitivity to insulin, but does not restore acetylcholine-activated endothelium-dependent vasodilation in DH rats.

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Effects of vitamin C on muscle glycogen and oxidative events in experimental diabetes

2006

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In the study, 38 male adult Wistar Albino rats with weights 200 +/- 20 g were used by separating them into four groups: Control, Vitamin C, Diabetes, Diabetes + Vitamin C. Body weights and fasting blood glucose were measured at the beginning and end of the experiment. AA, TBARS, GSH, NOx and glycogen levels of soleus muscles, and AA level of blood were measured. The results were compared using Anova variance and Mann-Whitney U tests. Results showed that AA levels in blood increased with vitamin C administration; AA, GSH and NOx levels in the muscle were low and MDA and glycogen levels were high in diabetics; and that vitamin C in the given dosage partially corrected these values. These results indicate that higher dosage than daily 20 mg/kg Vitamin C is required for being effective on metabolic and oxidizing events in diabetic rats.

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Effect of diabetes on aortic nitric oxide synthesis in spontaneously hypertensive rats; does captopril modulate this effect?

Cited by 8 publications

References 47 publications

Cystathionine-γ lyase-derived hydrogen sulfide mediates the cardiovascular protective effects of moxonidine in diabetic rats

Cystathionine-γ lyase-derived hydrogen sulfide mediates the cardiovascular protective effects of moxonidine in diabetic rats

Protein Kinase C inhibition ameliorates functional endothelial insulin resistance and Vascular Smooth Muscle Cell hypersensitivity to insulin in diabetic hypertensive rats

Effects of vitamin C on muscle glycogen and oxidative events in experimental diabetes

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