Insulin, thyroid hormone, and heart function of diabetic spontaneously hypertensive rat.

Davidoff, Amy J.; Rodgers, Robert L.

doi:10.1161/01.hyp.15.6.633

Cited by 17 publications

(15 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It has been suggested that the increase in MABP with age is a normal age-dependent process that may be a compensatory mechanism for loss of arterial compliance (4). Similarly, the decrease in HR is usually attributed to a diminution in the efficacy of ␤-adrenergic stimulation of the heart, which again is normal and an age-dependent process (41,43) The depressed MABP and HR in diabetic rats observed in the present study is in agreement with many other studies in STZ diabetic rats (9,14,18,20,23,31,39,44). Previous studies from our own laboratory have shown lower HR and reduced systolic blood pressure in conscious STZ-induced diabetic rats (44).…”

Section: Discussionsupporting

confidence: 91%

“…Despite an impairment of endothelial function and reduced bioavailability of endothelium-derived NO, streptozotocin (STZ)-induced diabetic rats are not hypertensive but instead are normotensive or hypotensive (9,14,18,20,23,31,39,44). In addition, an increased dependence on a functional NO system at the onset of diabetes has been reported to prevent the development of hypertension in STZ diabetic rats (12).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Increased expression of iNOS is associated with endothelial dysfunction and impaired pressor responsiveness in streptozotocin-induced diabetes

Nagareddy¹,

Xia²,

McNeill³

et al. 2005

American Journal of Physiology-Heart and Circulatory Physiology

138

View full text Add to dashboard Cite

(MABP) and heart rate (HR), endothelial dysfunction, and attenuated pressor responses to vasoactive agents. We investigated whether these abnormalities are due to diabetes-associated activation of inducible nitric oxide synthase (iNOS). In addition, the effect of the duration of diabetes on these abnormalities was also evaluated. Diabetes was induced by administration of 60 mg/kg STZ via the tail vein. One, 3, 9, or 12 wk after STZ injection, MABP, HR, and endothelial function were measured in conscious unrestrained rats. Pressor response curves to bolus doses of methoxamine (MTX) and angiotensin II (ANG II) were constructed in the presence of N- [3(aminomethyl)benzyl]-acetamidine, dihydrochloride (1400W), a specific inhibitor of iNOS. Depressed MABP and HR and impairment of endothelial function were observed as early as 3 wk after induction of diabetes. Acute inhibition of iNOS with 1400W (3 mg/kg iv) restored the attenuated pressor responses to both MTX and ANG II without affecting the basal MABP and HR. Immunohistochemical and Western analysis blot studies in cardiovascular tissues revealed decreased expression of endothelial nitric oxide synthase (eNOS) concomitant with increased expression of iNOS and nitrotyrosine with the progression of diabetes. Our findings suggest that induction of iNOS in cardiovascular tissues is dependent on the duration of diabetes and contributes significantly to the depressed pressor responses to vasoactive agents and potentially to endothelial dysfunction. inducible nitric oxide synthase; nitric oxide; cardiovascular abnormalities CHRONIC HYPERGLYCEMIA has been shown to directly affect the composition and structure of cardiac, vascular, and renal tissues, the progressive modification of which results in a deranged cardiovascular homeostasis (8). Cardiovascular depression, characterized by depressed mean arterial blood pressure (MABP), heart rate (HR), and attenuated pressor responses to vasoactive agents is one of the most notable manifestations of this derangement, particularly in animal models of Type 1 diabetes. Although the exact mechanisms by which diabetes contributes to cardiovascular depression are currently unknown, it is likely that hyperglycemia may initiate this abnormality through the activation of protein kinase C, increased activity of the polyol pathway, formation of nonenzymatic advanced glycosylation end products, oxidative stress, and/or possibly by induction of nitric oxide (NO) synthase (NOS) (19,42).The role of NO in the regulation of hemodynamics under hyperglycemic conditions has been controversial. Despite an impairment of endothelial function and reduced bioavailability of endothelium-derived NO, streptozotocin (STZ)-induced diabetic rats are not hypertensive but instead are normotensive or hypotensive (9,14,18,20,23,31,39,44). In addition, an increased dependence on a functional NO system at the onset of diabetes has been reported to prevent the development of hypertension in STZ diabetic rats (12). It has been suggested that increased NO synthesis m...

show abstract

Section: Discussionsupporting

confidence: 91%

mentioning

confidence: 99%

Increased expression of iNOS is associated with endothelial dysfunction and impaired pressor responsiveness in streptozotocin-induced diabetes

Nagareddy¹,

Xia²,

McNeill³

et al. 2005

American Journal of Physiology-Heart and Circulatory Physiology

138

View full text Add to dashboard Cite

show abstract

“…Diabetes increased T p of both SHR and WKY rat hearts but increased T r and reduced P^ and LV-dP/dt only in the SHR. None of these changes was associated with differences in coronary flow or resistance, either within or between strains, confirming previous observations 1120 ' 22 (data not shown).…”

Section: Left Ventricular Pressure Wave Characteristicssupporting

confidence: 91%

Ventricular relaxation of diabetic spontaneously hypertensive rat.

1990

Self Cite

View full text Add to dashboard Cite

Diabetes, and possibly the hypothyroidism that attends diabetes, impairs mechanical relaxation of ventricular muscle, in part by depressing the rate of Ca 2+ uptake by sarcoplasmic reticulum. Left ventricular hypertrophy exacerbates the adverse effects of diabetes on cardiac performance, but its effects on relaxation variables have not been well characterized. We examined the impact of streptozotocin-induced diabetes (8 weeks) on ventricular pressure load-dependent relaxation and sarcoplasmic reticular calcium uptake of hearts from spontaneously hypertensive rats and Wistar-Kyoto rats. Subsets of diabetic hypertensive rats were treated with either insulin (10 units/kg/day) or triiodothyronine (8-10 /tg/kg/day). Diabetes impaired load-dependent relaxation and depressed sarcoplasmic reticular calcium uptake only in spontaneously hypertensive rat hearts. Either insulin or triiodothyronine treatment prevented the diabetes-induced depressions of both mechanical and biochemical indexes of relaxation. The results suggest that 1) hypertrophic ventricles of spontaneously hypertensive rats are more susceptible to the detrimental effects of diabetes on relaxation indexes than are the nonhypertrophic Wistar-Kyoto rat ventricles, and 2) the hypothyroidism that attends diabetes may contribute to the impaired relaxation of diabetic spontaneously hypertensive rat left ventricle. have an impact on ventricular relaxation. The presence of LVH alone may or may not be associated with impaired relaxation. "17 However, when diabetes coexists with LVH in the spontaneously hypertensive rat (SHR), the rate of left ventricular pressure decline of perfused hearts is more profoundly depressed when compared with the effects of diabetes in normotensive rat strains. -13 Isometric relaxation is also prolonged in hypertrophic papillary muscles from the diabetic renovascular hypertensive rat.12 These results would suggest that combined effects of diabetes and LVH on SR Ca 2+ uptake might be more pronounced than the influence of either condition individually. However, the interaction between diabetes and LVH on the relation between myocardial relaxation and SR calcium uptake has not been characterized.Reduced serum levels of thyroid hormones are often associated with diabetes, l *-n and this hypothyroidism (or "low thyroid state") may contribute to diabetic cardiomyopathy. Thyroid hormone deficiencies, like diabetes, can lead to prolonged relaxation and depressed rates of SR calcium uptake in the myocardium. 18- 19 The effects of hypothyroidism on these measurements are well correlated, both in nonhypertrophic and hypertrophic ventricles. 20 Treatment of the diabetic SHR with triiodothyronine (T 3 ) effectively prevents the resultant cardiac dysfunction, 21 -22 but the influence of T 3 treatment in nonhypertensive diabetic rat models is inconsistent.

show abstract

“…To investigate the possible progressive effects of uncontrolled diabetes, animals were euthanized at two time points: 6-and 12-wk post-STZ treatment. To control for the MHC isoform shifts known to confound the study of rat cardiac tissue, a separate group of young animals that express 100% ␣-MHC was treated for short periods of time (0,6,11,16,21, and 42 days) with propylthiouracil (PTU; 0.8 g/l in the drinking water) to induce various amounts of ␤-MHC protein expression. Right ventricular trabeculae from these hearts were used experimentally to define the relationship between ␤-MHC protein expression, tension cost, and force development.…”

Section: Methodsmentioning

confidence: 99%

Depressed cardiac tension cost in experimental diabetes is due to altered myosin heavy chain isoform expression

Rundell¹,

Geenen²,

Buttrick³

et al. 2004

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

Rundell, Veronica L. M., David L. Geenen, Peter M. Buttrick, and Pieter P. de Tombe. Depressed cardiac tension cost in experimental diabetes is due to altered myosin heavy chain isoform expression. Am J Physiol Heart Circ Physiol 287: H408 -H413, 2004. First published March 4, 2004 10.1152/ajpheart.00049.2004.-Cardiac disease in diabetes presents as impaired left ventricular contraction and relaxation; however, the mechanisms underlying contractile protein dysfunction during the progression of disease are unknown. Accordingly, we assessed Ca 2ϩ -dependent tension development and tension-dependent ATP consumption (tension cost) in a rat model early (6 wk) and late (12 wk) after the onset of diabetes (50 mg/kg iv streptozotocin) using mechanical force-and enzyme-coupled UV absorbance measurements. Myofilament Ca 2ϩ sensitivity and maximal tension were unchanged between groups at either time point. Cross-bridge cycling rate was significantly decreased in diabetes, as indexed by tension cost (early control 5.4 Ϯ 0.4 and early diabetes 4.2 Ϯ 0.3; and late control 6.0 Ϯ 0.2 and late diabetes 4.2 Ϯ 0.2; P Ͻ 0.05). Because rodent models of cardiac disease are confounded by altered myosin isoform distribution, myosin content was determined by SDS-PAGE and densitometry. The cardiac content of ␣-myosin in diabetes was decreased to 41% Ϯ 4.1 at 6 wk and 32.5% Ϯ 2.9 at 12 wk of diabetes (early control 77.8% Ϯ 3.3 and late control 73.6% Ϯ 2.5). Separate control experiments demonstrated a linear decrease in tension cost with decreased ␣-myosin content. Given this, the depression of tension cost in this rodent model of diabetes could be fully explained by the altered myosin isoform distribution.cross-bridge cycling; cardiac energetics DIABETES MELLITUS is associated with a cardiomyopathy (CM), which develops in the absence of underlying coronary vascular disease in humans and rodents (12,26). This CM is associated with impaired left ventricular contraction and relaxation (4,22). Because diabetes affects Ͼ15 million Americans and approximately ϳ75% of these individuals will die of cardiovascular disease, it is important to ascertain what specific contractile deficits are present in diabetic CM.Accordingly, models of experimental diabetes have been generated to explore the molecular alterations that occur in diabetic CM. In brief, excitation-contraction coupling and the kinetics of shortening and relaxation are generally depressed in these preparations, regardless of peak shortening defects (17,23,24). In terms of the energetics of contraction, cross-bridge cycling and Ca 2ϩ sensitivity of Ca 2ϩ -dependent actin-activated MgATPase have been reported to be altered in diabetes (17,18). Alterations in maximal tension development have not been described; however, controversy exists with regard to Ca 2ϩ sensitivity of myofilaments in multicellular preparations (1, 17). Likewise, in isolated single cell preparations there have been reports of normal (17, 24), increased (28), and decreased peak shortening (23). Thus diabetic myocardium...

show abstract

Insulin, thyroid hormone, and heart function of diabetic spontaneously hypertensive rat.

Cited by 17 publications

References 42 publications

Increased expression of iNOS is associated with endothelial dysfunction and impaired pressor responsiveness in streptozotocin-induced diabetes

Increased expression of iNOS is associated with endothelial dysfunction and impaired pressor responsiveness in streptozotocin-induced diabetes

Ventricular relaxation of diabetic spontaneously hypertensive rat.

Depressed cardiac tension cost in experimental diabetes is due to altered myosin heavy chain isoform expression

Contact Info

Product

Resources

About