Influence of the endothelium on contractile responses of arteries from diabetic rats

doi:10.1016/0014-2999(88)90587-0

European Journal of Pharmacology

Volume 153, Issue 1, 9 August 1988, Pages 55-64

https://doi.org/10.1016/0014-2999(88)90587-0 Get rights and content

Abstract

Contractile responses of aortas and mesentric arteries from control and 3 month streptozotocin-diabetic rats to α-adrenoceptor agonists were compared in the presence and absence of endothelium. In the presence of endothelium, responses of both arteries from diabetic animals to norepinephrine and methoxamine were enhanced compared to control, although no response to clonidine could be detected in arteries from either control or diabetic animals. Following endothelium removal, no significant differences were found between control and diabetic arteries in maximum contractile responses to noradrenaline or methoxamine. However, the sensitivity (pD₂) of diabetic aortas to these two agonists was significantly increased, while maximum responses of diabetic aortas and mesenteric arteries to clonidine were much greater than control. In addition, no differences between control and diabetic aortas were detected when cGMP levels were measured in the absence and presence of acetylcholine. These results suggest that enhanced responsiveness of arteries from diabetic animals to α-adrenoceptor stimulation is not the result of a decrease in endothelium-derived relaxing factor (EDRF) release in diabetic blood vessels.

References (20)

B.W. Arbogast et al.
Injury of arterial endothelial cells in diabetic, sucrose-fed and aged rats
Atherosclerosis
(1984)
T.M. Griffith et al.
Evidence that cyclic guanosine monophosphate (cGMP) mediates endothelium-dependent relaxation
European J. Pharmacol.
(1985)
K. Murakami et al.
Role of endothelium in the contractions induced by norepinephrine and clonidine in rat aorta
Jap. J. Pharmacol.
(1985)
Y. Oyama et al.
Attenuation of endothelium-dependent relaxation in aorta from diabetic rats
European J. Pharmacol.
(1986)
I. Wakabayashi et al.
Modulation of the vascular tonus by the endothelium in experimental diabetes
Life Sci.
(1987)
P. Weidmann et al.
Sodium-volume factor, cardiovascular reactivity and hypotensive mechanism of diuretic therapy in mild hypertension associated with diabetes mellitus
Am. J. Med.
(1979)
A.R. Christlieb et al.
Vascular reactivity to angiotensin II and to norepinephrine in diabetic subjects
Diabetes
(1976)
J.A. Colwell et al.
Vascular disease in diabetes
Arch. Int. Med.
(1979)
C. Egleme et al.
Enhanced responsiveness of rat isolated aorta to clonidine after removal of the endothelial cells
Br. J. Pharmacol.
(1984)
R.F. Furchgott
Role of endothelium in responses of vascular smooth muscle
Circ. Res.
(1983)

There are more references available in the full text version of this article.

Cited by (105)

Effects of taurine on the reactivity of aortas from diabetic rats
2008, Life Sciences
The effects of the semi-essential amino acid-like nutrient, taurine, on alterations in the reactivities of aortas from male rats with chronic streptozotocin-induced diabetes were examined under in vitro conditions. In the absence of taurine, the contractile responsiveness of endothelium-denuded aortic rings from diabetic rats to norepinephrine, but not KCl, was enhanced compared to controls. This effect of norepinephrine on the diabetic rat aorta appeared to be associated with increased release of intracellular calcium, influx of extracellular calcium and protein kinase C-mediated responses. Incubation of endothelium-denuded aortic rings with 10 mM, but not 5 mM, taurine for 2 h reduced the augmented contractile responses of the tissues from diabetic rats to norepinephrine close to control levels, and this was associated with inhibition of responses linked to the release and influx of calcium, and protein kinase C activation. Endothelium-dependent relaxation of aortas from diabetic rats to acetylcholine was depressed relative to controls. This effect of diabetes was ameliorated close to control levels by incubating the tissues with 10 mM, but not 5 mM, taurine for 2 h. Incubation of nondiabetic rat aortic rings with 45 mM glucose for 3 h caused enhancement of contraction of the vascular smooth muscle to phenylephrine and impairment of endothelium-mediated vasorelaxation to acetylcholine, as compared to control responses. Co-incubation of the tissues with 5–10 mM taurine concentration-dependently reduced the alterations in both contractile and relaxant responses caused by high glucose. Overall, the data suggest that taurine ameliorates or prevents vascular reactivity alterations in diabetes. Such an observation provides preliminary evidence for taurine's potential as a therapeutic agent for the prevention or amelioration of vascular disorders in diabetes.
Carvedilol ameliorates endothelial dysfunction in streptozotocin-induced diabetic rats
2007, European Journal of Pharmacology
The beta-blocker, carvedilol has an additional endothelium-dependent vasodilating properties in patients with hypertension or heart failure. Whether carvedilol can improve endothelium-dependent relaxation in a diabetic animal model and its mechanism of action are unknown. The aim of this study was to investigate the effect of carvedilol on the endothelial-response of aortas from diabetic rats and the underlying mechanism. Acetylcholine-induced endothelium-dependent relaxation, sodium nitroprusside (SNP)-induced endothelium-independent relaxation, and expression of nitric oxide synthase 3 (NOS3) mRNA were measured in aortas isolated from both non-diabetic and streptozotocin-induced diabetic rats. The level of NO in serum was also measured 5 weeks after carvedilol administration (1 or 10 mg/kg/day). Endothelium-dependent relaxation declined along with the decrease of serum NO level in aortas from diabetic rats. Treatment with carvedilol for 5 weeks prevented the inhibition of endothelium-dependent relaxation and the decrease of serum NO levels caused by diabetes. The expression of NOS3 mRNA, protein expression and NOS3 phosphorylation at Ser1177 in diabetic rat aorta was very low in untreated diabetic aortas compared with the healthy group. Administration of carvedilol not only significantly increased the expression of NOS3 mRNA but also protein expression and NOS3 phosphorylation at Ser1177 in the healthy and diabetic groups. In conclusion, chronic carvedilol administration significantly ameliorated the endothelial dysfunction in diabetic rat aortas, in which increased NO level, up-regulated NOS3 mRNA and phosphorylation at Ser1177 may be involved.
A high-sodium diet in streptozotocin-induced diabetic rats impairs endothelium-derived hyperpolarizing factor-mediated vasodilation
2007, Journal of Pharmacological Sciences
We examined endothelium-derived hyperpolarizing factor (EDHF)-mediated relaxation of mesenteric arteries in high-sodium loaded streptozotocin (STZ)-induced diabetic rats. The study shows that acetylcholine (ACh)-induced, EDHF-mediated relaxation is relatively maintained in STZ-induced diabetic rats, but after a high-sodium diet was given, the function was significantly impaired in STZ-induced diabetic rats.
Alteration of aortic function from streptozotocin-diabetic rats with Kilham's virus is associated with inducible nitric oxide synthase
2006, Veterinary Journal
Kilham’s rat virus (KRV) is a parvovirus commonly known to affect laboratory rats. Qualitative immunohistochemical analysis revealed that aorta isolated from KRV-infected streptozotocin (STZ)-induced diabetic adult rats expressed markedly greater levels of inducible nitric oxide synthase (iNOS) than aorta from KRV-infected controls. In contrast with the prevailing literature, nitric oxide-mediated endothelium-dependent relaxation to acetylcholine was not blunted by STZ-diabetes, but was comparable to relaxations of aorta from controls. However, with increasing ex vivo duration, a decreased response to acetylcholine was observed in the STZ-diabetic aorta. In addition, whereas contraction responses to phenylephrine were not significantly altered over time in control tissue, aorta from STZ-diabetic rats developed increased tensions. The data suggest that increased iNOS-derived nitric oxide masks expected acetylcholine-mediated relaxation deficits as a result of KRV-infection, and that the deficit is unmasked by iNOS turnover ex vivo.
The effect of agmatine on the vascular reactivity in streptozotocin-diabetic rats
2003, Pharmacological Research
Aim: We investigated the vascular effects of agmatine (decarboxylated arginine=AGM), an endogenous ligand for α₂-adrenoceptors and imidazoline receptors, present in endothelium and smooth muscle, using the diabetic rat aortae.
Materials and methods: Studies were performed in control group (0.2 ml i.p. saline, n=10), streptozotocin (STZ)-diabetic control group (60 mg kg⁻¹ STZ i.p., n=10), agmatine (AGM)-control group (5 mg kg⁻¹ day⁻¹ i.p. AGM for 1 month, n=10), citrate-control group (0.2 ml 0.01 M, n=10), insulin-treated diabetic group ((3 U kg⁻¹ NPH+1 U kg⁻¹ regular insulin) twice per day, for 1 month, n=10) and AGM-treated diabetic group (5 mg kg⁻¹ day⁻¹ i.p. for 1 month, n=10). All values are expressed as means±S.E.M. Statistical analysis of the data was performed using ANOVA followed by Tukey multiple comparisons test.
Results: One-month AGM-treatment significantly decreased the blood glucose levels of diabetic rats (502±44 mg dl⁻¹ to 343±31 mg dl⁻¹, P<0.001). Fast, slow and total components of responses to noradrenaline in all the experimental groups were not significantly affected by AGM-treatment. AGM reversed the decreased responses of acetylcholine (pD₂ and Inh.%, P<0.001 and P<0.05) in diabetic rats although it did not affect the responses of sodium nitroprusside in all groups. The contraction values of KCl in all groups were not affected by AGM-treatment.
Conclusion: AGM-treatment could improve the increased blood glucose level, reverse the endothelial dysfunction and normalize the endothelium-dependent relaxation responses in STZ-diabetic rats.
Beneficial effect of aqueous garlic extract on the vascular reactivity of streptozotocin-diabetic rats
2003, Journal of Ethnopharmacology
The present study evaluated the beneficial effect of aqueous extract of garlic (Allium sativum L.; 100 mg/kg/day) on the alterations in vascular reactivity of streptozotocin-diabetic rats. After 8 weeks of treatment, thoracic aortic rings of rats were mounted in organ baths and contractile responses to phenylephrine and relaxant responses to acetylcholine and isosorbide dinitrate were assessed. Induction of diabetes significantly increased contractile responses to phenylephrine and impaired endothelium-dependent relaxations to acetylcholine in aortic rings, but did not change endothelium-independent relaxation to isosorbide dinitrate. Garlic administration significantly improved the impaired endothelium-dependent relaxations and decreased the enhanced contractile response to phenylephrine in diabetic rats. It is concluded that intraperitoneal administration of aqueous garlic extract can improve endothelial dysfunction in insulin-dependent model of uncontrolled diabetes.

View all citing articles on Scopus

^☆: This work was supported by a grant from the Medical Research Council of Canada.

²: Canadian Heart Foundation Scholar.

View full text

Influence of the endothelium on contractile responses of arteries from diabetic rats☆

Abstract

Atherosclerosis

European J. Pharmacol.

Jap. J. Pharmacol.

European J. Pharmacol.

Life Sci.

Am. J. Med.

Vascular reactivity to angiotensin II and to norepinephrine in diabetic subjects

Diabetes

Vascular disease in diabetes

Arch. Int. Med.

Enhanced responsiveness of rat isolated aorta to clonidine after removal of the endothelial cells

Br. J. Pharmacol.

Role of endothelium in responses of vascular smooth muscle

Circ. Res.