Vasoreactivity and prostacyclin release in streptozotocin‐diabetic rats: effects of insulin or aldose reductase inhibition

Stevens, Elizabeth; Willars, Gary B.; Lidbury, Paul S.; House, F.R.; Tomlinson, David R.

doi:10.1111/j.1476-5381.1993.tb13717.x

Cited by 12 publications

(5 citation statements)

References 42 publications

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“…These results suggest that the observed alteration in nitrergic neurotransmission is due to the production of a diabetic state by STZ and is not due to any non-specific effect of STZ itself. This is in agreement with numerous studies using other smooth muscle preparations where the effects of STZ-induced diabetes have been reversed or prevented by insulin treatment (Nowak et al, 1986;Longhurst et al, 1991;Hodgson & King, 1992;Stevens et al, 1993).…”

Section: Discussionsupporting

confidence: 92%

Effect of diabetes and elevated glucose on nitric oxide‐mediated neurotransmission in rat anococcygeus muscle

Way

Reid

1995

British J Pharmacology

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Nitric oxide (NO)‐mediated neurotransmission is impaired in anococcygeus muscle from 8‐week streptozotocin‐induced diabetic rats. This study investigated the effects of insulin treatment, and the duration of diabetes on this impairment. In addition, the effect of in vitro exposure to elevated glucose has been investigated on NO‐mediated relaxations, in muscles from untreated rats. Relaxant responses to field stimulation (0.5‐5 Hz, 10 s train), sodium nitroprusside (SNP; 5 and 10 nM) and NO (1 and 3 μM) were significantly impaired in anococcygeus muscles from 8‐week diabetic rats, compared to responses from control rats. Insulin treatment (5 u Lente day−1, s.c.) of diabetic rats prevented the development of this impairment. Consistent with findings in 8‐week diabetic rats, relaxations induced by field stimulation, SNP and NO were attenuated in tissues from 2‐week and 4‐week diabetic rats compared to corresponding control responses, whereas relaxations to papaverine (3 and 10 μM) were not reduced. In contrast, diabetes of 3‐days duration did not affect relaxations to field stimulation, SNP or NO. Incubation of anococcygeus muscles from untreated rats in medium containing elevated glucose (44.1 mM) for 6 h, significantly impaired relaxations to field stimulation compared to responses obtained after normal glucose (11.1 mM) incubation. Relaxations to SNP and to NO were not affected by 6h exposure to elevated glucose. Similarly, incubation in hyperosmolar solutions containing mannose or sucrose for 6 h, impaired relaxations to field stimulation, but not to SNP or NO. The results indicate that the diabetes‐induced impairment of NO‐mediated neurotransmission in the rat anococcygeus muscle develops between 3 days and 2 weeks after the induction of diabetes with streptozotocin. Prevention of the impairment by insulin treatment suggests that it is specific for the diabetic state. In addition, the impairment may be related to hyperglycaemia and the consequent rise in osmolarity, since in vitro exposure to high glucose as well as to other hyperosmolar media impaired NO‐mediated relaxations to field stimulation.

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Section: Discussionsupporting

confidence: 92%

Effect of diabetes and elevated glucose on nitric oxide‐mediated neurotransmission in rat anococcygeus muscle

Way

Reid

1995

British J Pharmacology

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“…With the data so far obtained, we cannot ascertain whether the changes observed are reversible, as reported for some biochemical parameters in experimental hyperglycaemia that were corrected to basal conditions [5,6,32].…”

Section: Discussionmentioning

confidence: 84%

Alterations of lung structure in experimental diabetes, and diabetes associated with hyperlipidaemia in hamsters

Popov¹,

Simionescu²

1997

Eur Respir J

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Alterations of lung structure in experimental diabetes, and diabetes associated with hyperlipidaemia in hamsters. D. Popov, M. Simionescu. ©ERS Journals Ltd 1997. ABSTRACT: Since hyperglycaemia is known to affect normal pulmonary physiology and biochemistry and few structure-function correlations have been reported, we designed experiments on hamsters subjected to streptozotocin-induced diabetes or diabetes associated with hyperlipidaemia, and investigated the impact of these conditions on the lung structure.At time intervals ranging 2-24 weeks from the inception of disease (without correcting blood glucose with insulin), the animals were sacrificed, and plasma glucose and cholesterol assayed. The lung was processed for electron microscopy, and the structural changes of the capillary and venular endothelium, of epithelial cells, and interstitium were examined.In diabetic animals, especially after 6 weeks of disease, a gradual narrowing of 35% of the capillaries and ~30% of the alveoli, and hyperplasia of the extracellular matrix, rich in collagen bundles, were observed. Frequently, capillaries contained adherent intravascular macrophages suggestive of an inflammatory process. The capillary endothelium was characterized by numerous plasmalemmal vesicles, often fused, well-developed synthesizing apparatus (endoplasmic reticulum and Golgi complex) and cytoskeleton, and an uneven distribution of the anionic sites on the luminal plasmalemma. The venular endothelium was particularly rich in Weibel-Palade bodies. The alveolar epithelium was often collapsed, compressing surfactant within the airspace. The lung interstitium was apparently enlarged, and the fibroblasts and contractile interstitial cells frequently contained lipid droplets. These alterations were more pronounced and occurred at a faster rate (4 weeks) in diabetes associated with hyperlipidaemia.The structural modifications reported in this study support the functional disturbances observed in association with hyperglycaemia, sustaining the conclusion that the lung is an organ affected by diabetes.

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“…Similarly, reports on diabetes-induced changes in PGI 2 production in the pulmonary circulation are also not consistent. In streptozotocin-treated rats, basal PGI 2 production and stimulated PGI 2 production in pulmonary circulation were reported to increase or to remain unchanged [ 14 , 19 , 20 ]. Interestingly, PGI 2 is a major regulator of the expression of thrombomodulin (CD141) [ 21 , 22 ], which complexes with thrombin (IIa) and activates protein C to act as an anticoagulant and endothelial protective mediator [ 23 ].…”

Section: Introductionmentioning

confidence: 99%

Comparison of Pulmonary and Systemic NO‐ and PGI₂‐Dependent Endothelial Function in Diabetic Mice

Fedorowicz

Buczek

Mateuszuk

et al. 2018

Oxidative Medicine and Cellular Longevity

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Diabetes increases the risk of pulmonary hypertension and is associated with alterations in pulmonary vascular function. Still, it is not clear whether alterations in the phenotype of pulmonary endothelium induced by diabetes are distinct, as compared to peripheral endothelium. In the present work, we characterized differences between diabetic complications in the lung and aorta in db/db mice with advanced diabetes. Male, 20-week-old db/db mice displayed increased HbA1c and glucose concentration compatible with advanced diabetes. Diabetic lungs had signs of mild fibrosis, and pulmonary endothelium displayed significantly ultrastructural changes. In the isolated, perfused lung from db/db mice, filtration coefficient (Kf,c) and contractile response to TXA2 analogue were enhanced, while endothelial NO-dependent modulation of pulmonary response to hypoxic ventilation and cumulative production of NO2− were impaired, with no changes in immunostaining for eNOS expression. In turn, 6-keto-PGF1α release from the isolated lung from db/db mice was increased, as well as immunostaining of thrombomodulin (CD141). In contrast to the lung, NO-dependent, acetylcholine-induced vasodilation, ionophore-stimulated NO2− generation, and production of 6-keto-PGF1α were all impaired in aortic rings from db/db mice. Although eNOS immunostaining was not changed, that of CD141 was clearly lowered. Interestingly, diabetes-induced nitration of proteins in aorta was higher than that in the lungs. In summary, diabetes induced marked ultrastructural changes in pulmonary endothelium that were associated with the increased permeability of pulmonary microcirculation, impaired NO-dependent vascular function, with compensatory increase in PGI2 production, and increased CD141 expression. In contrast, endothelial dysfunction in the aorta was featured by impaired NO-, PGI2-dependent function and diminished CD141 expression.

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Vasoreactivity and prostacyclin release in streptozotocin‐diabetic rats: effects of insulin or aldose reductase inhibition

Cited by 12 publications

References 42 publications

Effect of diabetes and elevated glucose on nitric oxide‐mediated neurotransmission in rat anococcygeus muscle

Effect of diabetes and elevated glucose on nitric oxide‐mediated neurotransmission in rat anococcygeus muscle

Alterations of lung structure in experimental diabetes, and diabetes associated with hyperlipidaemia in hamsters

Comparison of Pulmonary and Systemic NO‐ and PGI₂‐Dependent Endothelial Function in Diabetic Mice

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Vasoreactivity and prostacyclin release in streptozotocin‐diabetic rats: effects of insulin or aldose reductase inhibition

Cited by 12 publications

References 42 publications

Effect of diabetes and elevated glucose on nitric oxide‐mediated neurotransmission in rat anococcygeus muscle

Effect of diabetes and elevated glucose on nitric oxide‐mediated neurotransmission in rat anococcygeus muscle

Alterations of lung structure in experimental diabetes, and diabetes associated with hyperlipidaemia in hamsters

Comparison of Pulmonary and Systemic NO‐ and PGI2‐Dependent Endothelial Function in Diabetic Mice

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Comparison of Pulmonary and Systemic NO‐ and PGI₂‐Dependent Endothelial Function in Diabetic Mice