scholarly journals The expression and function of Ca2+ -sensing receptors in rat mesenteric artery; comparative studies using a model of type II diabetes

2008 ◽  
Vol 154 (3) ◽  
pp. 652-662 ◽  
Author(s):  
A H Weston ◽  
M Absi ◽  
E Harno ◽  
A R Geraghty ◽  
D T Ward ◽  
...  
2004 ◽  
Vol 82 (3) ◽  
pp. 175-182 ◽  
Author(s):  
Takayuki Matsumoto ◽  
Kentaro Wakabayashi ◽  
Tsuneo Kobayashi ◽  
Katsuo Kamata

We used the partial protection exerted by suitable dosages of nicotinamide against the β-cytotoxic effect of streptozotocin (STZ) to create an experimental diabetic syndrome in adult rats that appears closer to type II diabetes mellitus than other available animal models. The dosage of 230 mg/kg of nicotinamide given intraperitoneally 15 min before STZ administration (65 mg/kg i.v.) yielded animals with hyperglycemia (187.8 ± 17.8 vs. 103.8 ± 2.8 mg/dL in controls; P < 0.001) and preservation of plasma insulin levels. This study assessed the relationship between endothelial dysfunction and agonist-induced contractile responses in such rats. In the thoracic aorta, the acetylcholine (ACh) induced relaxation was significantly reduced and the noradrenaline (NA) induced contractile response was significantly increased in diabetic rats compared with age-matched control rats. In the superior mesenteric artery, the ACh-induced relaxation was similar in magnitude between diabetic and age-matched control rats; however, the ACh-induced endothelium-derived hyperpolarizing factor (EDHF) type relaxation was significantly weaker in diabetic rats than in the controls. The phenylephrine (PE) induced contractile response was not different between the two groups. The plasma concentration of NOx (NO2– + NO3–) was significantly lower in diabetic rats than in control rats. We conclude that vasomotor activities in conduit arteries are impaired in this type II diabetes model.Key words: aorta, contraction, endothelium-derived hyperpolarizing factor, endothelium-mediated relaxation, mesenteric artery, type II diabetes.


2018 ◽  
Vol 52 (3) ◽  
pp. 159-162 ◽  
Author(s):  
Johad Khoury ◽  
Elias Andrawus ◽  
Boaz Y. Bishop ◽  
Zaher S. Azzam

AbstractObjectives. Diabetes mellitus is an endemic disease of the current era. It is important to treat it properly. All antidiabetic medications have side effects and various safety profiles.Case report. Fifty-two years old patient with type II diabetes mellitus, who had spontaneous cutaneous and intra muscular bleeding after starting treatment with Exenatide. The patient’s history did not include any kind of spontaneous bleeding. Investigations did not reveal abnormal platelets count and function or coagulation profile. The use of the Exenatide was discontinued and during one year of follow-up, the patient did not experience an additional occurrence of spontaneous bleeding.Conclusions. To the best of our knowledge, this is the first report of spontaneous bleeding probably caused by Exenatide. The exact pathophysiology, by which the drug can cause spontaneous bleeding, is still not clear and has to be revealed.


2020 ◽  
Vol 11 ◽  
Author(s):  
Samuel N. Baldwin ◽  
Shaun L. Sandow ◽  
Gema Mondéjar-Parreño ◽  
Jennifer B. Stott ◽  
Iain A. Greenwood

Background and Purpose: Arterial diameter is dictated by the contractile state of the vascular smooth muscle cells (VSMCs), which is modulated by direct and indirect inputs from endothelial cells (ECs). Modulators of KCNQ-encoded kV7 channels have considerable impact on arterial diameter and these channels are known to be expressed in VSMCs but not yet defined in ECs. However, expression of kV7 channels in ECs would add an extra level of vascular control. This study aims to characterize the expression and function of KV7 channels within rat mesenteric artery ECs.Experimental Approach: In rat mesenteric artery, KCNQ transcript and KV7 channel protein expression were determined via RT-qPCR, immunocytochemistry, immunohistochemistry and immunoelectron microscopy. Wire myography was used to determine vascular reactivity.Key Results: KCNQ transcript was identified in isolated ECs and VSMCs. KV7.1, KV7.4 and KV7.5 protein expression was determined in both isolated EC and VSMC and in whole vessels. Removal of ECs attenuated vasorelaxation to two structurally different KV7.2-5 activators S-1 and ML213. KIR2 blockers ML133, and BaCl2 also attenuated S-1 or ML213-mediated vasorelaxation in an endothelium-dependent process. KV7 inhibition attenuated receptor-dependent nitric oxide (NO)-mediated vasorelaxation to carbachol, but had no impact on relaxation to the NO donor, SNP.Conclusion and Implications: In rat mesenteric artery ECs, KV7.4 and KV7.5 channels are expressed, functionally interact with endothelial KIR2.x channels and contribute to endogenous eNOS-mediated relaxation. This study identifies KV7 channels as novel functional channels within rat mesenteric ECs and suggests that these channels are involved in NO release from the endothelium of these vessels.


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