Alterations in aortic and tail artery reactivity to agonists after streptozotocin treatment

Ramanadham, Sasanka; Lyness, William H.; Tenner, Thomas E.

doi:10.1139/y84-066

Cited by 67 publications

(38 citation statements)

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“…It has been proposed that this is in part due to altered reactivity of vascular smooth muscle to neurotransmitters and circulating hormones (Weidmann et al, 1979). In an attempt to investigate this hypothesis, the responsiveness of vascular preparations from animals with chemically-induced diabetes to various vasoactive agents has been extensively studied (Brody & Dixon, 1964;Ramanadhan & Tenner, 1984;MacLeod & McNeill, 1985;Agrawal et al, 1987;White & Carrier, 1988). Although the results of these investigations appear to be controversial, previous studies from our laboratory have demonstrated that aortae and mesenteric arteries from male rats with streptozotocin (STZ)-induced diabetes of 12 weeks duration are more responsive to the contractile effects of noradrenaline (NA) than are the corresponding arteries from age-matched control rats (MacLeod, 1985;Harris & MacLeod, 1988).…”

Section: Introductionmentioning

confidence: 99%

Protein kinase C‐mediated contractile responses of arteries from diabetic rats

Abebe

MacLeod

1990

British J Pharmacology

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1 The role of protein kinase C (PKC) in mediating enhanced contractile responses of aortae and mesenteric arteries from male rats with 12-14 week streptozotocin-induced diabetes to noradrenaline (NA) was investigated using the PKC activator, phorbol 12,13-dibutyrate (PDB), and the PKC inhibitor, staurosporine. 2 Maximum contractile responses of aortae and mesenteric arteries from diabetic rats to NA were significantly enhanced compared with responses of arteries from age-matched control animals. The maximum NA responses were increased by 59.6 + 7.9% in aortae and by 54.9 + 7.4% in mesenteric arteries from diabetic animals, compared to their respective controls. 3 Pretreatment of aortae and mesenteric arteries from both control and diabetic animals with staurosporine (5 x 10 -8M) caused marked inhibition of contractile responses to a maximum concentration of NA (10-5M in aortae; 3 x 10 5M in mesenteric arteries). In the presence of staurosporine, no difference was observed in the magnitude of contractile responses of arteries from control and diabetic rats to NA. 4 Maximum contractile responses of mesenteric arteries from diabetic rats to PDB were significantly increased (by 45.0 + 4.9%) compared to responses of arteries from control animals. In contrast, no significant difference was found in the magnitude of contractile responses of aortae from control and diabetic rats to PDB. 5 Staurosporine (5 x 10-8M) caused marked attenuation of contractile responses of arteries from control and diabetic rats to a maximum concentration of PDB (3 x 10-6 M). In the presence of staurosporine, the difference in magnitude of contractile responses of mesenteric arteries from control and diabetic rats to PDB was abolished. 6 Contractile responses of aortae and mesenteric arteries from control and diabetic rats to PDB were reduced in the absence of extracellular Ca2", and in the presence of the Ca2 + channel blockers, nifedipine (3 x 10-6 M) or verapamil (3 x 10-6 M). Under these conditions, no difference was found in the magnitude of contractile responses of mesenteric arteries from control and diabetic rats to PDB. 7 These data suggest that enhanced contractile responses of aortae and mesenteric arteries from streptozotocin-induced diabetic rats to NA may result, at least in part, from increased activation of PKC. In addition, increased activation of PKC-mediated processes, which are dependent on the presence of extracellular Ca2+, may further contribute to the enhanced contractile responses of diabetic mesenteric arteries to NA.

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Section: Introductionmentioning

confidence: 99%

Protein kinase C‐mediated contractile responses of arteries from diabetic rats

Abebe

MacLeod

1990

British J Pharmacology

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“…Although the aetiology of vascular disorders in diabetes is not understood, it has been suggested that alterations in the sensitvity and/or responsiveness of vascular smooth muscle to neurotransmitters and circulating hormones may underlie the functional abnormalities of blood vessels in diabetes [5,6]. In this regard, the responsiveness of isolated vascular preparations from STZ or alloxan-diabetic rats has been studied extensively [7][8][9][10][11][12][13]. Although the results of these studies are somewhat inconclusive, the discrepancies might be attributed to differences in experimental conditions such as techniques for measuring contractile force, expression of contractile force, gender, and severity and duration of diabetes.…”

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confidence: 99%

The effect of vanadyl treatment on vascular responsiveness of streptozotocin-diabetic rats

et al. 1994

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Summary Vanadyl sulphate has been demonstrated to possess insulin-like effects in streptozotocin (STZ) diabetic rats, including the normalization of hyperglycaemia and the prevention of diabetes-induced cardiac dysfunction. However, the effectiveness of vanadyl sulphate on diabetes-related vascular aberrations has not been questioned. Hence, in the present work, we have specifically addressed the question of whether chronic oral vanadyl sulphate treatment has any beneficial effect on diabetes-induced changes in vascular reactivity. Male albino rats were injected with a single intravenous dose of STZ (55 mg/kg). Vanadyl sulphate was administered in the drinking water at a concentration of i mg/ml from 7 days after the STZ injection and treatment was maintained for 10 weeks. Vanadyl intake was accompanied by decreased blood glucose and serum insulin levels. The effects of diabetes on vascular smooth muscle function were assessed by the responsiveness of aortae to noradrenaline and KC1. Contractile responses of the diabetic aortae were found to be significantly increased as compared with controls. However, there were no significant differences in pD2 values of the agonists in either of the groups. Treatment of diabetic rats with vanadyl sulphate completely prevented the increases in responsiveness of aortae to noradrenaline and KC1. The effect of diabetes on the fast and slow components of noradrenaline-induced contraction was also examined. Both components of the response to noradrenaline were significantly increased in diabetic aortae. These changes were also prevented by vanadyl sulphate treatment. The data demonstrate that 10-week vanadyl sulphate treatment results in improved vascular reactivity of diabetic rats. [Diabetologia (1994) 37: 572-578]

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“…As a consequence, vascular disease has been considered a complicating feature of the diabetic state (2). Recently, attempts to investigate the functions of vascular smooth muscle in diabetes mellitus were carried out using animal diabetes models, either geneti cally derived (3,4) or chemically induced by alloxan (5-7) or streptozotocin (STZ,8,9) treatment. A significant decrease in pros tacyclin production (10) and an increase in sensitivity to noradrenaline (NA, 11) have been reported in the aorta of diabetic mice and rats.…”

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confidence: 99%

Diabetes-induced enhancement of prostanoid-stimulated contraction in mesenteric veins of mice.

et al. 1989

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Abstract-We investigated the influence of the diabetic state on the contractile response of longitudinal segments of isolated mesenteric vein to prostanoids and leukotriene (LT), and the contribution of the vascular endothelium to modulation of the contractile response was determined. The normal mesenteric vein and de endothelialized veins of normal (ddY), diabetic KK-CAY and streptozotocin ddY mice (150 mg/kg, i.v., 6 weeks) were used. In the diabetic state, the contractions produced by noradrendline (60 aM), high K+ solution (143.4 mM), and the thromboxane A2 analogue U-4661 9 (29 nM-29 mM) were not affected, and LTD4 (0.1 nM-1 ,uM)-induced contraction was suppressed. Contractions induced by prostaglandin (PG) E2 (0.2 ,aM-2 mM), PGF2a (0.3 tiM-0.3 mM) and the pros tacyclin derivatives PG12-Na (10-100 tM) and TRK-100 (0.2 ,aM-2_ mM) were significantly enhanced in the presence of an intact vascular endothelium, but not in de-endothelialized segments. The increase in PGF2a (0.28 mM) contractions was dependent on age (correlation coefficient r=0.36, significant difference, P< 0.05) and blood glucose (r=0.88, significant difference, P<0.01), but was in dependent of obesity. The contractile response to PGD2 (0.3-0.9 mM) was enhanced in both intact and de-endothelialized segments. These results indicate that the diabetic state affects prostanoid responses in an endothelium-dependent manner, except for the PGD2 response, which is independent of the endothelium.

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Alterations in aortic and tail artery reactivity to agonists after streptozotocin treatment

Cited by 67 publications

References 0 publications

Protein kinase C‐mediated contractile responses of arteries from diabetic rats

Protein kinase C‐mediated contractile responses of arteries from diabetic rats

The effect of vanadyl treatment on vascular responsiveness of streptozotocin-diabetic rats

Diabetes-induced enhancement of prostanoid-stimulated contraction in mesenteric veins of mice.

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