Influence of Gender and Diabetes on Vascular and Myocardial Contractile Function

Brown, Ronald C.; Walsh, Mary F.; Ren, Jun

doi:10.1081/erc-100107864

Cited by 29 publications

(30 citation statements)

References 27 publications

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“…However, we observed that endothelium-independent relaxation to SNP, an indicator of smooth muscle sensitivity to NO, was also clearly impaired 8 wk after the STZ injection in both sexes. This finding is in agreement with that of other investigators who also reported an impaired SNP-induced relaxation in diabetes (10,15). These data suggest that the responsiveness of vascular smooth muscle to NO is affected by STZ injection after 8 wk in both sexes.…”

Section: Vs C)supporting

confidence: 94%

Sex differences in mesenteric endothelial function of streptozotocin-induced diabetic rats: a shift in the relative importance of EDRFs

Zhang

Thor

Han

et al. 2012

American Journal of Physiology-Heart and Circulatory Physiology

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Rahimian R. Sex differences in mesenteric endothelial function of streptozotocin-induced diabetic rats: a shift in the relative importance of EDRFs. Am J Physiol Heart Circ Physiol 303: H1183-H1198, 2012. First published September 14, 2012 doi:10.1152 doi:10. /ajpheart.00327.2012 studies suggest that diabetes affects male and female vascular beds differently. However, the mechanisms underlying the interaction of sex and diabetes remain to be investigated. This study investigates whether there are 1) sex differences in the development of abnormal vascular responses and 2) changes in the relative contributions of endothelium-derived relaxing factors in modulating vascular reactivity of mesenteric arteries taken from streptozotocin (STZ)-induced diabetic rats at early and intermediate stages of the disease (1 and 8 wk, respectively). We also investigated the mesenteric expression of the mRNAs for endothelial nitric oxide (NO) synthase (eNOS) and NADPH oxidase (Nox) in STZ-induced diabetes in both sexes. Vascular responses to acetylcholine (ACh) in mesenteric arterial rings precontracted with phenylephrine were measured before and after pretreatment with indomethacin (cyclooxygenase inhibitor), N -nitro-L-arginine methyl ester (NOS inhibitor), or barium chloride (Kir blocker) plus ouabain (Na ϩ -K ϩ -ATPase inhibitor). We demonstrated that ACh-induced relaxations were significantly impaired in mesenteric arteries from both male and female diabetic rats at 1 and 8 wk. However, at 8 wk the extent of impairment was significantly greater in diabetic females than diabetic males. Our data also showed that in females, the levels of eNOS, Nox2, and Nox4 mRNA expression and the relative importance of NO to the regulation of vascular reactivity were substantially enhanced, whereas the importance of endotheliumderived hyperpolarizing factor (EDHF) was significantly reduced at both 1 and 8 wk after the induction of diabetes. This study reveals the predisposition of female rat mesenteric arteries to vascular injury after the induction of diabetes may be due to a shift away from a putative EDHF, initially the major vasodilatory factor, toward a greater reliance on NO.sex; diabetes; mesenteric arteries; nitric oxide; endothelium-derived hyperpolarizing factor CARDIOVASCULAR DISEASES (CVDs) are the major causes of morbidity and mortality in patients with diabetes mellitus. Several reports including our recent studies (30,31,36) suggest that hyperglycemia and diabetes affect male and female vascular beds differently. Clinically, premenopausal women have a lower incidence of CVDs compared with age-matched men. However, premenopausal women with diabetes not only lose this sex-based cardiovascular protection but also have a higher risk of CVDs than men (4,20,71). Nonetheless, there is insufficient evidence to establish the mechanism(s) underlying the loss of this female-specific cardiovascular protection in premenopausal patients with diabetes.Endothelial dysfunction is an early sign of diabetic vascular diseases. Endothelial dysfuncti...

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Section: Vs C)supporting

confidence: 94%

Sex differences in mesenteric endothelial function of streptozotocin-induced diabetic rats: a shift in the relative importance of EDRFs

Zhang

Thor

Han

et al. 2012

American Journal of Physiology-Heart and Circulatory Physiology

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“…This is consistent with our previous studies using multicellular papillary muscles and ventricular myocytes from chemically-induced diabetic rats (4,8). The reduced maximum velocity of shortening and relengthening associated with prolonged duration of shortening and relengthening may be resulted from the myosin heavy chain isoenzyme shift from V 1 to V 3 in diabetes (18).…”

Section: Discussionsupporting

confidence: 81%

“…Consistent with our previous study on ventricular papillary muscles (8), diabetes ablated the gender-specific difference in myocardial function. There was no significant difference in contraction or relaxation parameters between the two genders under diabetic state.…”

Section: Discussionsupporting

confidence: 80%

“…Recent clinical, epidemiological and experimental evidence has convincingly suggested that there is a gender bias in the progression of diabetic cardiomyopathy. In general, while difference in cardiac rhythm and arrhyathmia exists between genders, premenopausal women are much less susceptible to heart failure, and display much more favorable myocardial adaptation to hemodynamic overload both in contractile function and hypertrophic reserve (8)(9)(10)(11)(12)(13)(14). However, this ''gender-bias'' or ''female advantage'' may be significantly dampened with the onset of diabetes in pre-menopausal women (15).…”

Section: Introductionmentioning

confidence: 82%

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Influence of Gender on Intrinsic Contractile Properties of Isolated Ventricular Myocytes from Calmodulin‐Induced Diabetic Transgenic Mice

Zhang

Duan

et al. 2003

Endocrine Research

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Diabetes mellitus impairs ventricular function, which itself may be disparately influenced by gender. This study compared the impact of gender on cardiac contractile response in ventricular myocytes from wild-type FVB and calmodulin-induced diabetic transgenic (OVE26) mice at young (2 month) and older (11 month) age. Mechanical and intracellular Ca 2þ properties of cardiac myocytes were evaluated using an IonOptix MyoCam 1 system. Diabetic mice of both genders exhibited significantly elevated blood glucose regardless of age. OVE26 myocytes displayed reduced peak shortening (PS) and maximal velocity of shortening=relengthening (AEdL=dt), and prolonged time-to-PS (TPS) and time-to-90% relengthening (TR 90 ), associated with higher resting intracellular Ca 2þ levels and attenuated Ca 2þ -induced intracellular Ca 2þ release compared with the FVB myocytes. Peak shortening and AEdL=dt were smaller in female FVB groups when compared to the age-matched male counterparts. However, these gender differences were ablated by the diabetic state. No significant gender-related differences in intracellular Ca 2þ handling were noted in either FVB or OVE26 myocytes, with the exception of overt gender differences in OVE26 mice when age was taken into account. Young female OVE26 mice exhibited better-preserved mechanical function while older female OVE26 mice displayed the worst mechanical function among all four OVE26 groups. In conclusion, our data confirmed impaired cardiac contractile function in diabetes, partially due to altered intracellular Ca 2þ handling, in both genders. Mechanical differences existed between genders but were ''cancelled off'' by diabetic state. Nevertheless, a ''female advantage'' in ventricular function may still persist in young female diabetic subjects.

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“…This implies that diabetes is detrimental to cardiomyocytes, independent of macrovascular complications. Results from chemically induced insulinopenic (2) and genetically predisposed insulin-resistant (3) rodent models (4) as well as human histological (5) and clinical observations (6) provide support for this concept of a specific diabetic cardiomyopathy.…”

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confidence: 98%

Catalase Protects Cardiomyocyte Function in Models of Type 1 and Type 2 Diabetes

et al. 2004

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Many diabetic patients suffer from a cardiomyopathy that cannot be explained by poor coronary perfusion. Reactive oxygen species (ROS) have been proposed to contribute to this cardiomyopathy. Consistent with this we found evidence for induction of the antioxidant genes for catalase in diabetic OVE26 hearts. To determine whether increased antioxidant protection could reduce diabetic cardiomyopathy, we assessed cardiac morphology and contractility, Ca 2؉ handling, malondialdehyde (MDA)-modified proteins, and ROS levels in individual cardiomyocytes isolated from control hearts, OVE26 diabetic hearts, and diabetic hearts overexpressing the antioxidant protein catalase. Diabetic hearts showed damaged mitochondria and myofibrils, reduced myocyte contractility, slowed intracellular Ca 2؉ decay, and increased MDA-modified proteins compared with control myocytes. Overexpressing catalase preserved normal cardiac morphology, prevented the contractile defects, and reduced MDA protein modification but did not reverse the slowed Ca 2؉ decay induced by diabetes. Additionally, high glucose promoted significantly increased generation of ROS in diabetic cardiomyocytes. Chronic overexpression of catalase or acute in vitro treatment with rotenone, an inhibitor of mitochondrial complex I, or thenoyltrifluoroacetone, an inhibitor of mitochondrial complex II, eliminated excess ROS production in diabetic cardiomyocytes. The structural damage to diabetic mitochondria and the efficacy of mitochondrial inhibitors in reducing ROS suggest that mitochondria are a source of oxidative damage in diabetic cardiomyocytes. We also found that catalase overexpression protected cardiomyocyte contractility in the agouti model of type 2 diabetes. These data show that both type 1 and type 2 diabetes induce damage at the level of individual myocytes, and that this damage occurs through mechanisms utilizing ROS.

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Influence of Gender and Diabetes on Vascular and Myocardial Contractile Function

Cited by 29 publications

References 27 publications

Sex differences in mesenteric endothelial function of streptozotocin-induced diabetic rats: a shift in the relative importance of EDRFs

Sex differences in mesenteric endothelial function of streptozotocin-induced diabetic rats: a shift in the relative importance of EDRFs

Influence of Gender on Intrinsic Contractile Properties of Isolated Ventricular Myocytes from Calmodulin‐Induced Diabetic Transgenic Mice

Catalase Protects Cardiomyocyte Function in Models of Type 1 and Type 2 Diabetes

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