Chronic verapamil treatment attenuates the negative inotropic effect of ethanol in diabetic rat myocardium

Brown, Ronald C.; Bhasin, Prashant; Savage, Adedapo O.; Dunbar, Joseph C.

doi:10.1139/y94-141

Cited by 11 publications

(5 citation statements)

References 24 publications

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“…The experimental procedures were approved by Wayne State University School of Medicine Animal Investigation Committee and have been previously ORDER REPRINTS described (9). Briefly, male and female Wistar rats ($210 g) were made diabetic via a single i.v.…”

Section: Experimental Animalsmentioning

confidence: 99%

Influence of Gender and Diabetes on Vascular and Myocardial Contractile Function

2001

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Premenopausal women have a lower cardiovascular risk than men or postmenopausal women. However, this "female advantage" is lost in diabetes, a condition characterized by cardiac and vascular contractile dysfunction. This study was designed to compare the influence of diabetes on vascular and myocardial contractile function between genders. Adult male and female rats were made diabetic with streptozotocin (55 mg/kg) and maintained for 8 weeks. Tension development was examined in thoracic aortic rings and left ventricular papillary muscles. KCl-induced vasoconstriction, acetylcholine (ACh)-induced endothelium dependent or sodium nitroprusside (SNP)-induced endothelium-independent vasorelaxation, duration and maximal velocity of myocardial contraction and relaxation duration (TPT/RT90 and +/- VT) were similar between males and females. Diabetes augmented KCl-induced vasoconstriction at low doses, reduced SNP-induced vasorelaxation and had little effect on ACh-induced vasorelaxation in aortic rings from both genders. Diabetes prolonged TPT and RT90 in both genders, and reduced +/- VT in males but not females. Acute increase in extracellular Ca2+ (2.7 mM to 5.4 mM) shortened TPT in diabetic myocardium from both genders, whereas it had no effect on other myocardial mechanical indices in normal or diabetic groups of either gender. In addition, acute exposure to the Na+/K(+)-ATPase inhibitor ouabain shortened TPT/RT90 and enhanced +/- VT in myocardium from normal female, whereas it had no effect on male or diabetic myocardium. In conclusion, these data suggest that in the vasculature, there is no difference in diabetes-induced contractile dysfunction between genders, however several gender-specific differences are evident in the myocardium.

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Section: Experimental Animalsmentioning

confidence: 99%

Influence of Gender and Diabetes on Vascular and Myocardial Contractile Function

2001

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“…Section 1734 solely to indicate this fact. 0363-6135/98 $5.00 Copyright 1998 the American Physiological Society H823 (2)(3)(4). After 5-7 days of untreated diabetes, animals were euthanized under ketamine-xylazine sedation (3:1, 1.32 mg/kg ip).…”

Section: Animalsmentioning

confidence: 99%

“…Tension development of papillary muscles was measured with a force transducer (model F-30, Hugo Sachs, March-Hugstetten, Germany), as described previously (2)(3)(4). After euthanasia, hearts were rapidly excised and immersed in oxygenated (95% O 2 -5% CO 2 ) Tyrode solution (in mM: 5.4 KCl, 136.9 NaCl, 11.9 NaHCO 3 , 0.50 MgCl 2 , 2.70 CaCl 2 , 0.45 NaH 2 PO 4 , 5.6 glucose, pH 7.4) at 37°C.…”

Section: Tension Measurement Of Papillary Musclementioning

confidence: 99%

“…Clinically, this diabetes-induced myopathic state is associated mainly with impaired diastolic function (25). In experimental diabetes the mechanical properties of myocardium and cardiomyocytes in vitro are significantly altered, characterized by prolongation of contraction and relaxation as well as a marked slowing in relaxation velocity (3,4,10,23). These diabetesinduced alterations have been attributed to biochemical and ultrastructural anomalies, in particular, impaired intracellular Ca 2ϩ homeostasis involving reduced sarcoplasmic Ca 2ϩ -ATPase activity (19).…”

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Altered inotropic response to IGF-I in diabetic rat heart: influence of intracellular Ca²⁺and NO

Ren

Walsh

Hamaty

et al. 1998

American Journal of Physiology-Heart and Circulatory Physiology

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Normally, insulin-like growth factor I (IGF-I) exerts positive effects on cardiac growth and myocardial contractility, but resistance to its action has been reported in diabetes. This study was designed to determine whether IGF-I-induced myocardial contractile action is altered in diabetes as a result of an intrinsic alteration of contractile properties at the cellular level. Contractile responses to IGF-I were examined in left ventricular papillary muscles and ventricular myocytes from normal and short-term (5–7 days) streptozotocin-induced diabetic rats. Mechanical properties of muscles and myocytes were evaluated using a force transducer and an edge detector, respectively. Preparations were electrically stimulated at 0.5 Hz, and contractile properties analyzed include peak tension development (PTD) or peak twitch amplitude (PTA), time to peak contraction/shortening, and time to 90% relaxation/relengthening. Intracellular Ca2+ transients were measured as fura 2 fluorescence intensity changes. IGF-I (1–500 ng/ml) caused a dose-dependent increase in PTD and PTA in preparations from normal but not diabetic animals. IGF-I did not alter time to peak contraction/shortening or time to 90% relaxation/relengthening. Pretreatment with the NO synthase inhibitor N ω-nitro-l-arginine methyl ester (100 μM) attenuated IGF-I-induced increases in PTD in normal myocardium but unmasked a positive inotropic action in diabetic animals. Pretreatment with N ω-nitro-l-arginine methyl ester blocked IGF-I-induced increases in PTA in single myocytes. Consistent with its inotropic actions on muscles and myocytes, IGF-I induced a dose-dependent increase in Ca2+transients in normal but not diabetic myocytes. These results suggest that the IGF-I-induced inotropic response is depressed in diabetes because of an intrinsic alteration at the myocyte level. Mechanisms underlying this alteration in IGF-I-induced myocardial response may be related to changes in intracellular Ca2+ and/or NO production in diabetes.

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“…The maximum dose of rats in this experiment was 48 mg/kg/day, which was obtained by converting the maximum adult dose of verapamil according to the human-rat dose conversion formula [ 30 ]. For the dose range of 4-48 mg/kg/day, the drug doses used in verapamil treatment of diabetic rats in the literatures were used as reference, 12 mg/kg/day and 24 mg/kg/day were selected as the median values to achieve a reasonable dose range [ 31 , 32 ]. Finally, 4/12/24/48 mg/kg/day were selected as the drug doses for rats in this study, and the corresponding drug doses for adults were 40/120/240/480 mg/day.…”

Section: Methodsmentioning

confidence: 99%

Effect of verapamil on bone mass, microstructure and mechanical properties in type 2 diabetes mellitus rats

Gong

et al. 2022

BMC Musculoskelet Disord

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Background Verapamil was mainly used to treat hypertension, cardiovascular disease, inflammation and improve blood glucose in patients with diabetes, but its effects on bone mass, microstructure and mechanical properties were unclear. This study described the effects of verapamil on bone mass, microstructure, macro and nano mechanical properties in type 2 diabetic rats. Methods Rat models of type 2 diabetes were treated with verapamil at doses of 4, 12, 24 and 48 mg/kg/day by gavage respectively, twice a day. After 12 weeks, all rats were sacrificed under general anesthesia. Blood glucose, blood lipid, renal function and biochemical markers of bone metabolism were obtained by serum analysis, Micro-CT scanning was used to assess the microstructure parameters of cancellous bone of femoral head, three-point bending test was used to measure maximum load and elastic modulus of femoral shaft, and nano-indentation tests were used to measure indentation moduli and hardnesses of longitudinal cortical bone in femoral shaft, longitudinal and transverse cancellous bones in femoral head. Results Compared with T2DM group, transverse indentation moduli of cancellous bones in VER 24 group, longitudinal and transverse indentation moduli and hardnesses of cancellous bones in VER 48 group were significantly increased (p < 0.05). Furthermore, the effects of verapamil on blood glucoses, microstructures and mechanical properties in type 2 diabetic rats were dependent on drug dose. Starting from verapamil dose of 12 mg/kg/day, with dose increasing, the concentrations of P1NP, BMD, BV/TV, Tb. Th, Tb. N, maximum loads, elastic moduli, indentation moduli and hardnesses of femurs in rats in treatment group increased gradually, the concentrations of CTX-1 decreased gradually, but these parameters did not return to the level of the corresponding parameters of normal rats. Verapamil (48 mg/kg/day) had the best therapeutic effect. Conclusion Verapamil treatment (24, 48 mg/kg/day) significantly affected nano mechanical properties of the femurs, and tended to improve bone microstructures and macro mechanical properties of the femurs, which provided guidance for the selection of verapamil dose in the treatment of type 2 diabetic patients.

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Chronic verapamil treatment attenuates the negative inotropic effect of ethanol in diabetic rat myocardium

Cited by 11 publications

References 24 publications

Influence of Gender and Diabetes on Vascular and Myocardial Contractile Function

Influence of Gender and Diabetes on Vascular and Myocardial Contractile Function

Altered inotropic response to IGF-I in diabetic rat heart: influence of intracellular Ca²⁺and NO

Effect of verapamil on bone mass, microstructure and mechanical properties in type 2 diabetes mellitus rats

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Chronic verapamil treatment attenuates the negative inotropic effect of ethanol in diabetic rat myocardium

Cited by 11 publications

References 24 publications

Influence of Gender and Diabetes on Vascular and Myocardial Contractile Function

Influence of Gender and Diabetes on Vascular and Myocardial Contractile Function

Altered inotropic response to IGF-I in diabetic rat heart: influence of intracellular Ca2+and NO

Effect of verapamil on bone mass, microstructure and mechanical properties in type 2 diabetes mellitus rats

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Altered inotropic response to IGF-I in diabetic rat heart: influence of intracellular Ca²⁺and NO