Reducing Arginase Activity via Dietary Manganese Deficiency Enhances Endothelium-Dependent Vasorelaxation of Rat Aorta

Ensunsa, Jodi L.; Symons, J. David; Lanoue, Louise; Schrader, Heather R; Keen, Carl L.

doi:10.1177/153537020422901109

Cited by 24 publications

(11 citation statements)

References 42 publications

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“…Arginase activity is also sensitive to Mn tissue concentration (33). A recent study by Ensunsa et al (34) demonstrates that dietary Mn deficiency in rats reduces arginase activity and enhances endothelium-dependent vasorelaxation in rat aorta. However, whether or not overexposure to Mn affects arginase activity and results in the opposite effect remains unknown.…”

Section: Effect Of Mn On Arginaseor Ca-mediated Vasoconstrictionmentioning

confidence: 99%

Cardiovascular Toxicities Upon Manganese Exposure

Jiang

Zheng

2005

118

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Manganese (Mn)-induced Parkinsonism has been well documented; however, little attention has been devoted to Mn-induced cardiovascular dysfunction. This review summarizes literature data from both animal and human studies on Mn's effect on cardiovascular function. Clinical and epidemiological evidence suggests that the incidence of abnormal electrocardiogram (ECG) is significantly higher in Mn-exposed workers than that in the control subjects. The main types of abnormal ECG include sinus tachycardia, sinus bradycardia, sinus arrhythmia, sinister megacardia, and ST-T changes. The accelerated heartbeat and shortened P-R interval appear to be more prominent in female exposed workers than in their male counterparts. Mn-exposed workers display a mean diastolic blood pressure that is significantly lower than that of the control subjects, especially in the young and female exposed workers. Animal studies indicate that Mn is capable of quickly accumulating in heart tissue, resulting in acute or sub-acute cardiovascular disorders, such as acute cardiodepression and hypotension. These toxic outcomes appear to be associated with Mn-induced mitochondrial damage and interaction with the calcium channel in the cardiovascular system.

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Section: Effect Of Mn On Arginaseor Ca-mediated Vasoconstrictionmentioning

confidence: 99%

Cardiovascular Toxicities Upon Manganese Exposure

Jiang

Zheng

2005

118

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“…Remaining tissue from the base was snap-frozen in liquid nitrogen for later RNA extraction, quantitative RT-PCR, and Western immunoblotting (described below). Finally, the thoracic aorta and femoral artery, which were immersed in iced PSS during the coronary artery dissections, were isolated and used to measure vascular reactivity (6,9,19,(21)(22)(23).…”

Section: Methodsmentioning

confidence: 99%

Knockout of insulin receptors in cardiomyocytes attenuates coronary arterial dysfunction induced by pressure overload

Symons

Hu²,

Yang³

et al. 2011

American Journal of Physiology-Heart and Circulatory Physiology

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Ablating insulin receptors in cardiomyocytes causes subendocardial fibrosis and left ventricular (LV) dysfunction after 4 wk of transverse aortic constriction (TAC).To determine whether these maladaptive responses are precipitated by coronary vascular dysfunction, we studied mice with cardiomyocyterestricted knock out of insulin receptors (CIRKO) and wild-type (WT) TAC mice before the onset of overt LV dysfunction. Two weeks of TAC produced comparable increases (P Ͻ 0.05 vs. respective sham) in heart weight/body weight (mg/g) in WT-TAC (8.03 Ϯ 1.14, P Ͻ 0.05 vs. respective sham) and CIRKO-TAC (7.76 Ϯ 1.25, P Ͻ 0.05 vs. respective sham) vs. WT-sham (5.64 Ϯ 0.11) and CIRKO-sham (4.64 Ϯ 0.10) mice. In addition, 2 wk of TAC were associated with similar LV geometry and function (echocardiography) and interstitial fibrosis (picrosirius red staining) in CIRKO and WT mice. Responses to acetylcholine (ACh), N G -monomethyl-L-arginine (L-NMMA), and sodium nitroprusside (SNP) were measured in coronary arteries that were precontracted to achieve ϳ70% of maximal tension development using the thromboxane A2 receptor mimetic U-46619 (ϳ3 ϫ 10 Ϫ6 M). ACh-evoked vasorelaxation was absent in WT-TAC but was present in CIRKO-TAC albeit reduced relative to sham-operated animals. L-NMMA-evoked tension development was similar in vessels from CIRKO-TAC mice but was lower (P Ͻ 0.05) in WT-TAC animals vs. the respective sham-operated groups, and SNP-evoked vasorelaxation was similar among all mice. Thus estimates of stimulated and basal endothelial nitric oxide release were better preserved in CIRKO vs. WT mice in response to 2 wk of TAC. These findings indicate that maladaptive LV remodeling previously observed in CIRKO-TAC mice is not precipitated by coronary artery dysfunction, because CIRKO mice exhibit compensatory mechanisms (e.g., increased eNOS transcript and protein) to maintain coronary endothelial function in the setting of pressure overload. nitric oxide; blood vessel; mice; cardiac hypertrophy; endotheliumdependent vasorelaxation DIABETIC PATIENTS WITH CARDIOVASCULAR disease (CVD) have a worse prognosis than nondiabetic individuals who develop CVD (7). Even when the extent of coronary artery disease and infarct size are accounted for, diabetic patients have a higher incidence of heart failure and mortality in the setting of acute coronary syndromes or revascularization procedures. Although the precise mechanism responsible for the poor outcome of diabetic patients in these situations is unclear, insulin resistance and hyperglycemia may each play significant roles.Both cardiac myocytes and vascular endothelial cells may be adversely affected by diabetes, particularly in the setting of pathological stresses such as ischemia or pressure overload. Hyperglycemia and altered insulin signaling may independently or collectively have negative consequences in the vasculature (3,5,14,21). In addition, growing evidence suggests that cardiac myocytes may affect the coronary vasculature through paracrine mechanisms (12).To elucidate the ad...

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“…Total nitrates/nitrites as an estimate of nitric oxide concentration in tissues, was determined by a commercial assay (Stressgen, Assay Design, Ann Arbor, MI). Arginase activity in liver was determined as previously described (23). Protein concentrations were determined with a commercial kit (BioRad Laboratories, Richmond, CA).…”

Section: Methodsmentioning

confidence: 99%

Rat Strains Bred for Low and High Aerobic Running Capacity Do Not Differ in Their Survival Time to Hemorrhage

Klemcke

Ryan

Britton³

et al. 2009

Exp Biol Med (Maywood)

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Hemorrhagic shock reflects low tissue perfusion that is inadequate to maintain normal metabolic functions. Often associated with this condition are impairments in cellular oxygen delivery and utilization. Rat strains divergent in their running endurance have been artificially selected over 12 generations. As these rats bred for high (HCR) vs low (LCR) aerobic running capacity have greater tissue O2 utilization capacity and improved cardiovascular function, we hypothesized that HCR would be more tolerant (i.e., have greater survivability) to the global ischemia of hemorrhagic shock than LCR. To address this hypothesis, survival time to a severe --as substantiated by dramatic changes in plasma lactate, HCO3, and base deficit--controlled hemorrhage was measured. Male rats were catheterized and, ∼ 24 hours later, an estimated > 35% of the calculated blood volume was removed during a 26 min period while the rats were conscious and unrestrained. Rats were observed for 6 hr or until death. Contrary to our hypothesis, survival time in HCR (220 ± 63 min; n=6) did not differ statistically (P = 0.46) from that in LCR (279 ± 53 min; n=7). Similarly, there were no statistical differences (P ≥ 0.08) between rat lines in blood pH, lactate, HCO3, and base deficit pre or post-hemorrhage. In addition, few significant differences between lines in response to hemorrhage were detected by measures of cellular antioxidant status in heart, liver or lung. Since animals with genetically greater tissue oxygen utilization capacity failed to show longer survival times, our results suggest that other mechanisms must play a more dominant role in determining survivability to hemorrhage under conditions of this hemorrhage.

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Reducing Arginase Activity via Dietary Manganese Deficiency Enhances Endothelium-Dependent Vasorelaxation of Rat Aorta

Cited by 24 publications

References 42 publications

Cardiovascular Toxicities Upon Manganese Exposure

Cardiovascular Toxicities Upon Manganese Exposure

Knockout of insulin receptors in cardiomyocytes attenuates coronary arterial dysfunction induced by pressure overload

Rat Strains Bred for Low and High Aerobic Running Capacity Do Not Differ in Their Survival Time to Hemorrhage

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