scholarly journals Arterial pressure lability is improved by sodium-glucose cotransporter 2 inhibitor in streptozotocin-induced diabetic rats

2017 ◽  
Vol 40 (7) ◽  
pp. 646-651 ◽  
Author(s):  
Tomoko Yoshikawa ◽  
Takuya Kishi ◽  
Keisuke Shinohara ◽  
Ko Takesue ◽  
Risa Shibata ◽  
...  
2021 ◽  
Vol 22 (15) ◽  
pp. 7774
Author(s):  
Sevil Korkmaz-Icöz ◽  
Cenk Kocer ◽  
Alex A. Sayour ◽  
Patricia Kraft ◽  
Mona I. Benker ◽  
...  

Vascular ischemia/reperfusion injury (IRI) contributes to graft failure and adverse clinical outcomes following coronary artery bypass grafting. Sodium-glucose-cotransporter (SGLT)-2-inhibitors have been shown to protect against myocardial IRI, irrespective of diabetes. We hypothesized that adding canagliflozin (CANA) (an SGLT-2-inhibitor) to saline protects vascular grafts from IRI. Aortic rings from non-diabetic rats were isolated and immediately mounted in organ bath chambers (control, n = 9–10 rats) or underwent cold ischemic preservation in saline, supplemented either with a DMSO vehicle (IR, n = 8–10 rats) or 50µM CANA (IR + CANA, n = 9–11 rats). Vascular function was measured, the expression of 88 genes using PCR-array was analyzed, and feature selection using machine learning was applied. Impaired maximal vasorelaxation to acetylcholine in the IR-group compared to controls was significantly ameliorated by CANA (IR 31.7 ± 3.2% vs. IR + CANA 51.9 ± 2.5%, p < 0.05). IR altered the expression of 17 genes. Ccl2, Ccl3, Ccl4, CxCr4, Fos, Icam1, Il10, Il1a and Il1b have been found to have the highest interaction. Compared to controls, IR significantly upregulated the mRNA expressions of Il1a and Il6, which were reduced by 1.5- and 1.75-fold with CANA, respectively. CANA significantly prevented the upregulation of Cd40, downregulated NoxO1 gene expression, decreased ICAM-1 and nitrotyrosine, and increased PECAM-1 immunoreactivity. CANA alleviates endothelial dysfunction following IRI.


1987 ◽  
Vol 65 (8) ◽  
pp. 1615-1618 ◽  
Author(s):  
R. H. Alper ◽  
H. J. Jacob ◽  
M. J. Brody

Deafferentation of sinoaortic baroreceptors produces a marked increase in the lability of arterial pressure that is sustained chronically. Studies reviewed in this paper were designed to determine the mechanisms responsible for generating arterial pressure lability. Pharmacological interruption of the humoral vasopressin and angiotensin systems failed to alter arterial pressure lability. In contrast, blockade of sympathetic nervous system transmission at both ganglionic and alpha-adrenergic receptor levels significantly attenuated lability. A similar effect was observed with the peripheral neurotoxin, 6-hydroxydopamine. After blockade of sympathetic transmission, a further reduction in lability was produced by blocking the renin–angiotensin or vasopressin systems. The dissociation of the level of arterial pressure from lability was achieved with parachloroamphetamine which raised arterial pressure but reduced lability. A substantial peripheral contribution to lability was obtained in experiments in which the alpha-adrenergic agonist, phenylephrine, produced a marked increase in lability in both normal and baroreceptor-denervated animals in which humoral and neural transmission were blocked. These data demonstrate that following baroreceptor deafferentation, arterial pressure lability is produced primarily by the sympathetic nervous system and secondarily by circulating humoral factors that appear to act on vascular smooth muscle to induce fluctuations in the level of arterial pressure.


QJM ◽  
2020 ◽  
Vol 113 (Supplement_1) ◽  
Author(s):  
S F Ewida ◽  
A M H Shabaan ◽  
H F Eldomiaty ◽  
G S Y Hanna ◽  
S E Hassabelnabi ◽  
...  

Abstract Background Cardiovascular disease is the most life-threatening diabetic complication. Type II diabetes may lead to damage of the heart muscle. Sodium glucose cotransporter 2 (SGL2) inhibitors are a new class of diabetic medications indicated only for the treatment of type II diabetes. Aim This investigation was assigned to compare the effect of metformin and SGL2 inhibitors (dapaglifilizone) in type II diabetic rats. Design and methods: Eighty rats divided into four groups were used: non diabetic; diabetic; diabetic metformin -treated; diabetic dapagliflizoline- treated. At the end, arterial blood pressure and cardiac performance (cardiac contractility and heart rate) were assessed. Serum glucose, glycosylated hemoglobin (HbA1c), insulin, lipid profile, total antioxidant capacity, malondialdehyde, tumor necrosis factor α were measured. HOMA-IR index was calculated. DNA changes were assessed from hearts and aortea. Aortic endothelial changes recorded using H&E and masson trichome techniques. Results Glycemic index, lipid profile, oxidative stress and inflammatory parameters were significantly improved in both metformin and dapagliflizoline treated groups with also significant improvement in blood pressure, Cardiac performance and reduction in collagen deposition in aortic tissue and DNA fragmentation. Dapagliflizoline treatment results were significantly improved in all parameters compared to metformin treatment. Conclusion SGL2 inhibitors (dapaglifilizone) successfully restored glycemic state, cardiac performance, DNA and endothelial changes in type II diabetic rats compared to metformin.


2002 ◽  
Vol 35 (7) ◽  
pp. 843-849 ◽  
Author(s):  
P. Dall'Ago ◽  
V.O.K. Silva ◽  
K.L.D. De Angelis ◽  
M.C. Irigoyen ◽  
R. Fazan Jr. ◽  
...  

1997 ◽  
Vol 11 (S1) ◽  
pp. 94s-94s
Author(s):  
Y Bézie ◽  
P Challande ◽  
E Glaser ◽  
B Lucet ◽  
M Safar ◽  
...  

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