Role of extracellular Ca2+ in the selective enhancement of contractile responses of arteries from diabetic rats to noradrenaline

1994 ◽  
Vol 72 (12) ◽  
pp. 1544-1551 ◽  
Author(s):  
Worku Abebe ◽  
Kim Howard Harris ◽  
Kathleen M. MacLeod
Keyword(s):  
Matched Control ◽  
Diabetic Rats ◽  
Mesenteric Arteries ◽  
Percentage Change ◽  
Contractile Responses ◽  
Similar Percentage ◽  
Selective Enhancement ◽  
Channel Agonist

Maximum contractile responses of diabetic aortas incubated in the absence of extracellular Ca2+ to increasing Ca2+ (0.01–10 mM) in the presence of 1 μM noradrenaline, but not 40 mM KCl, were significantly increased compared with those of age-matched control rats. Maximum contractile responses of both aortas and mesenteric arteries from diabetic rats to noradrenaline, but not KCl, in the presence of extracellular Ca2+ (2.5 mM) were also significantly enhanced. The Ca2+ channel antagonists verapamil and nifedipine and the Ca2+ channel agonist BAY K8644 produced a similar percentage change in the magnitude of the noradrenaline response in arteries from both control and diabetic rats. These data confirm the selective nature of the enhancement of contractile responses of arteries from diabetic rats to noradrenaline and suggest that this may be mediated in part through enhanced noradrenaline-induced influx of extracellular Ca2+ through channels sensitive to the Ca2+ channel ligands. However, this does not appear to be the only explanation for the enhanced contractile responses of diabetic arteries to noradrenaline, since in the presence of maximum concentrations of nifedipine (3 μM) and verapamil (10μM), responses of diabetic arteries to noradrenaline were still greater than those of control arteries.Key words: diabetes, arteries, contractility, noradrenaline, extracellular Ca2+.

Alterations in EDHF-type relaxation and phosphodiesterase activity in mesenteric arteries from diabetic rats

2003 ◽  
Vol 285 (1) ◽  
pp. H283-H291 ◽  
Author(s):  
Takayuki Matsumoto ◽  
Tsuneo Kobayashi ◽  
Katsuo Kamata
Keyword(s):  
Gap Junctions ◽  
Superior Mesenteric Artery ◽  
Mesenteric Artery ◽  
Matched Control ◽  
Diabetic Rats ◽  
Selective Inhibitor ◽  
Mesenteric Arteries ◽  
Phosphodiesterase Activity ◽  
Camp Phosphodiesterase

In isolated superior mesenteric artery rings from age-matched control rats and streptozotocin (STZ)-induced diabetic rats, we investigated the role of cAMP in endothelium-derived hyperpolarizing factor (EDHF)-type relaxation. The ACh-induced EDHF-type relaxation was significantly weaker in STZ-induced diabetic rats than in control rats, and in both groups of rats it was attenuated by 18α-glycyrrhetinic acid (18α-GA), an inhibitor of gap junctions, and enhanced by IBMX, a cAMP-phosphodiesterase (PDE) inhibitor. These enhanced EDHF-type responses were very similar in magnitude between diabetic and age-matched control rats. The EDHF-type relaxation was enhanced by cilostamide, a PDE3-selective inhibitor, but not by Ro 20–1724, a PDE4-selective inhibitor. The expression levels of the mRNAs and proteins for two cAMP PDEs (PDE3A, PDE3B) were significantly increased in STZ-induced diabetic rats, but those for PDE4D were not. We conclude that the impairment of EDHF-type relaxations in STZ-induced diabetic rats may be attributed to a reduction in the action of cAMP via increased PDE activity.

Vascular responses to agonists in rat mesenteric artery from diabetic rats

1987 ◽  
Vol 65 (7) ◽  
pp. 1484-1490 ◽  
Author(s):  
Devendra K. Agrawal ◽  
John H. McNeill
Keyword(s):  
Diabetic Rats ◽  
Isometric Tension ◽  
Mesenteric Arteries ◽  
Diabetic Rat ◽  
Prostaglandin E ◽  
Contractile Responses ◽  
Alpha Adrenoceptor ◽  
Diabetic Model ◽  
Rat Mesenteric Artery ◽  
Adrenoceptor Agonists

The effect of diabetes on vascular smooth muscle function was investigated in the muscular arteries from spontaneously and chemically induced diabetic rats. Isolated ring segments of superior mesenteric arteries from BB diabetic and streptozotocin (STZ)-diabetic rats (12 weeks after onset of diabetes) were used for isometric tension studies. Contractile responses to alpha-adrenoceptor agonists (norepinephrine, methoxamine, phenylephrine, B-HT 920, guanabenz, SKF 89748-A), serotonin, and K+ were significantly higher in STZ-diabetic rat arteries as compared with the controls. In spontaneously diabetic rat arteries only the contractile responses to the putatively selective alpha2-adrenoceptor agonists, K+ and prostaglandin E1, were significantly increased. pD2 values of the agonists in both groups of diabetic arteries were not significantly different from the respective controls. Nifedipine inhibited all contractile responses in a dose-dependent fashion. The responses to K+ and alpha2-adrenoceptor agonists were attenuated to a greater extent by nifedipine in both groups of diabetic blood vessels. The calcium channel activator, BAY K 8644, produced a twofold increase in force of contraction in streptozotocin-diabetic and spontaneously diabetic rat arteries as compared with the responses in their respective controls. These results suggest caution in extrapolating all the findings from the streptozotocin-induced diabetic model to the spontaneously diabetic model. However, increased activity of calcium channels in vascular muscle cells in both groups of diabetics may be responsible, at least in part, for the increased vascular contractility in diabetes mellitus.

Effect of streptozotocin diabetes on motor and inhibitory transmission in rat anococcygeus

1992 ◽  
Vol 70 (10) ◽  
pp. 1372-1378 ◽  
Author(s):  
G. N. Luheshi ◽  
M. A. Zar
Keyword(s):  
Matched Control ◽  
Streptozotocin Diabetes ◽  
Electrical Field Stimulation ◽  
Diabetic Rats ◽  
Field Stimulation ◽  
Response Curves ◽  
Electrical Field ◽  
Contractile Responses ◽  
Inhibitory Transmission ◽  
Adrenergic Transmission

The effect of streptozotocin diabetes of 4-week duration on the adrenergic motor transmission and on the nonadrenergic, noncholinergic, inhibitory transmission in the rat anococcygeus was investigated by recording contractile and relaxant activity of isolated muscle preparations taken from diabetic and age-matched control animals. The neurogenic contractile responses to electrical field stimulation were significantly reduced in the preparations from diabetic rats. The inhibitory transmission remained unaffected in the diabetic rats. Concentration–response curves showed no change in sensitivity of the diabetic anococcygei to noradrenaline. The maximum tension generated was also similar in preparations from diabetic and nondiabetic animals. The contractile responses to electrical field stimulation were significantly greater in preparations from diabetic rats treated for 4 weeks with either sorbinil (20 mg∙kg−1∙day−1 orally) or myo-inositol (667 mg∙kg−1∙day−1 orally) when compared with the untreated diabetic controls; the sensitivity to noradrenaline was identical in all three groups. It is concluded that streptozotocin diabetes causes a significant reduction of adrenergic contractile responses of the anococcygeus to electrical field stimulation by a prejunctional mechanism, and the reduction can be prevented by treating the animals with the aldose reductase inhibitor sorbinil or with myo-inositol.Key words: streptozotocin; autonomic neuropathy; adrenergic transmission; nonadrenergic, noncholinergic transmission; sorbinil; myo-inositol.

Role of nitrosative stress in early neuropathy and vascular dysfunction in streptozotocin-diabetic rats

2007 ◽  
Vol 293 (6) ◽  
pp. E1645-E1655 ◽  
Author(s):  
Irina G. Obrosova ◽  
Viktor R. Drel ◽  
Christine L. Oltman ◽  
Nazar Mashtalir ◽  
Jyoti Tibrewala ◽  
...  
Keyword(s):  
Nitrosative Stress ◽  
Vascular Dysfunction ◽  
Sensory Nerve ◽  
Triethylene Glycol ◽  
Monomethyl Ether ◽  
Diabetic Rats ◽  
Mesenteric Arteries ◽  
Dose Finding ◽  
Reactive Oxidant

Evidence for important roles of the highly reactive oxidant peroxynitrite in diabetic complications is emerging. We evaluated the role of peroxynitrite in early peripheral neuropathy and vascular dysfunction in STZ-diabetic rats. In the first dose-finding study, control and STZ-diabetic rats were maintained with or without the potent peroxynitrite decomposition catalyst Fe(III)tetrakis-2-( N-triethylene glycol monomethyl ether) pyridyl porphyrin (FP15) at 3, 5, or 10 mg·kg−1·day−1in the drinking water for 4 wk after an initial 2 wk without treatment for assessment of early neuropathy. In the second study with similar experimental design, control and STZ-diabetic rats were maintained with or without FP15, 5 mg·kg−1·day−1, for vascular studies. Rats with 6-wk duration of diabetes developed motor and sensory nerve conduction velocity deficits, mechanical hyperalgesia, and tactile allodynia in the absence of small sensory nerve fiber degeneration. They also had increased nitrotyrosine and poly(ADP-ribose) immunofluorescence in the sciatic nerve and dorsal root ganglia. All these variables were dose-dependently corrected by FP15, with minimal differences between the 5 and 10 mg·kg−1·day−1doses. FP15, 5 mg·kg−1·day−1, also corrected endoneurial nutritive blood flow and nitrotyrosine, but not superoxide, fluorescence in aorta and epineurial arterioles. Diabetes-induced decreases in acetylcholine-mediated relaxation by epineurial arterioles and coronary and mesenteric arteries, as well as bradykinin-induced relaxation by coronary and mesenteric arteries, were alleviated by FP15 treatment. The findings reveal the important role of nitrosative stress in early neuropathy and vasculopathy and provide the rationale for further studies of peroxynitrite decomposition catalysts in long-term diabetic models.

Diabetes-induced rat tracheal segment supersensitivity to carbachol

1988 ◽  
Vol 66 (5) ◽  
pp. 660-662 ◽  
Author(s):  
J. J. Mongold ◽  
G. H. Gros ◽  
A. Michel ◽  
J. H. McNeill ◽  
J. J. Serrano
Keyword(s):  
Matched Control ◽  
Smooth Muscles ◽  
Diabetic Rats ◽  
Contractile Responses ◽  
Single Intravenous Injection ◽  
Acting Insulin ◽  
Daily Dose ◽  
Group A ◽  
Long Acting ◽  
Group B

Contractile responses to carbachol of tracheal segments isolated (i) from rats made diabetic 4 months prior by a single intravenous injection (50 mg/kg) of streptozotocin (group B), and (ii) from diabetic rats that had been treated during the same period with a daily dose (2–4 U/animal) of long-acting insulin (group C) were compared with the contractile responses of trachea isolated from age-matched control animals (group A). Tracheal segments from group B were significantly more responsive to carbachol than those from group A or C at low, but not at high carbachol concentrations. Carbachol pD2 values were higher in group B (6.85 ± 0.05) than in groups A (6.46 ± 0.07) or C (6.37 ± 0.06), but were not significantly different between groups A and C. These data indicate that diabetes induces a supersensitivity to carbachol in airway smooth muscles, possibly related to a diabetes-induced vagal autonomic neuropathy.

scholarly journals Role of Prostaglandins in the Vasodilator Effect of the Aqueous Extract from Artemisia annua Plant in Streptozotocin-induced Diabetic Rats

2019 ◽  
pp. 1-10
Author(s):  
Forouzan Sadeghimahalli ◽  
Hossein Khaleghzadeh-Ahangar ◽  
Tourandokht Baluchnejadmojarad
Keyword(s):  
Aqueous Extract ◽  
Contractile Response ◽  
Artemisia Annua ◽  
Herbal Medicines ◽  
Vascular Complications ◽  
Diabetic Rats ◽  
Protective Effects ◽  
Contractile Responses ◽  
Vasodilator Effect

Aims: One of the most important causes of mortality is vascular complications resulting from diabetes mellitus. Herbal medicines are commonly used for the treatment of cardiovascular conditions in diabetes.  Artemisia annua (A. annua) as a medicinal plant has vasculature protective effects in diabetic rats. In the present study, the role of prostaglandins in the vasodilator effect of A. annua aqueous extract in diabetic rats has been studied. Study Design: This animal study was conducted on diabetic rats. Aqueous extract of Artemisia annua was used for diabetic rats. Then, isolated thoracic aortic rings were exposed to indomethacin and after exposure, the contractile responses were measured. Methodology: The studied animals were male Wistar rats (n=36) which were randomly divided into intact, untreated-diabetic, and A. annua aqueous extract treated-diabetic groups. For the induction of diabetes, streptozotocin was intraperitoneally (i.p.) administered (60 mg/kg). A. annua extract-treated group received i.p. 100 mg/kg of extract for one month. After one month, the dose contractile response of isolated aortic rings to phenylephrine (doses of 10-9-10-4 mol/L) in the absence and presence of indomethacin as a prostaglandins inhibitor was determined using isolated tissue setup. Results: Comparison of contractile responses before and after adding indomethacin in treated extract diabetic rats, showed that contractile responses of aorta ring with and without endothelium after adding indomethacin significantly increased at all concentrations of phenylephrine (P<0.05–P<0.0001) while indomethacin in diabetic rats did not effect on contractile response. Conclusions: Since the vasodilator effect of the aqueous extract of A. annua with a concentration of 100 mg/kg of body weight was pronounced even after endothelium removal, it can be claimed that the vasodilator effects of the extract are related to inhibition of prostaglandin generation both indirectly and directly.

Effects of endothelin receptor blockade on hypervasoreactivity in streptozotocin-diabetic rats: vessel-specific involvement of thromboxane A2

2006 ◽  
Vol 84 (8-9) ◽  
pp. 823-833 ◽  
Author(s):  
Emi Arikawa ◽  
Claudia Cheung ◽  
Inna Sekirov ◽  
Mary L. Battell ◽  
Violet G. Yuen ◽  
...  
Keyword(s):  
Vascular Function ◽  
Acute Effect ◽  
Diabetic Rats ◽  
Mesenteric Arteries ◽  
Receptor Blockade ◽  
Endothelin Receptor ◽  
Contractile Responses ◽  
In Vitro Incubation ◽  
Synthase Inhibitor

Increased vasoconstrictor response to norepinephrine (NE) and endothelin (ET)-1 in arteries from diabetic animals is ameliorated by chronic endothelin receptor blockade with bosentan and was absent in endothelium-denuded arteries, suggesting the involvement of ET-1 and an endothelium-derived contracting factor such as thromboxane A2 (TxA2). To examine this possibility, we determined the effects of acute blockade of ET receptors or inhibition of TxA2 synthesis on the vascular function of superior mesenteric arteries (SMA) and renal arteries (RA) isolated from nondiabetic and 11-week streptozotocin (STZ) diabetic rats chronically treated with either bosentan or vehicle. Both in vitro incubation with bosentan and a selective ETA receptor blocker, BQ123, eradicated the increase in NE contractile responses in diabetic SMA. Additionally, in vitro incubation with the thromboxane synthase inhibitor, dazmegrel, abrogated the exaggerated NE and ET-1 contractile responses in diabetic SMA. Conversely, in RA, no significant acute effect of bosentan, BQ123, nor dazmegrel on vascular responses to NE was observed. Dazmegrel incubation attenuated the maximum contractile responses to ET-1 in diabetic RA; however, these responses in diabetic RA remained significantly greater than those of other groups. Diabetic RA but not SMA exhibited an enhanced contractile response to the TxA2 analogue U46619, which was corrected by chronic bosentan treatment. Immunohistochemical analyses in diabetic SMA revealed an increase in ETA receptor level that was normalized by chronic bosentan treatment. These data indicate that an interaction between ET-1 and TxA2 may be involved in mediating the exaggerated vasoconstrictor responses in diabetic arteries. Furthermore, the underlying mechanisms appear to be vessel specific.

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