Tempol improves vascular function in the mesenteric vascular bed of senescent rats

2004 ◽  
Vol 82 (3) ◽  
pp. 200-207 ◽  
Author(s):  
R Tatchum-Talom ◽  
D S Martin

Ageing is associated with structural and functional alterations of the vasculature. The nature of age-related vascular disorders is not completely understood. Oxidative stress is hypothesized to play a crucial role in the pathophysiology of vascular complications. We investigated the effects of chronic treatment with the superoxide dismutase mimetic tempol (4-hydroxy-2,2,6,6-tetramethyl piperidinoxyl) on vascular function in the mesenteric vasculature of aged rats. Young (3 weeks) and old (40 weeks) Sprague–Dawley rats were treated with tempol (1 mM in drinking water) or vehicle for 3 weeks. Arterial blood pressure was slightly, but significantly, higher in old than in young rats. Tempol had no effect on arterial blood pressure. The vasoconstrictor responses to norepinephrine (NE) and serotonin (5-HT) were exaggerated in the mesenteric vascular bed (MVB) removed from old rats. Vasodilator responses to acetylcholine (ACh), papaverine (PPV), and isoprenaline (ISO) were reduced in the MVB of old rats in comparison with young rats. Chronic treatment of old rats with tempol normalized their responses to NE and 5-HT. The dilator responses to ACh, PPV, and ISO were similar between old rats receiving tempol and young rats. The present findings suggest that oxidative stress contributes to vascular dysfunction in the mesentery of old rats. The vasculoprotective effects of tempol remain to be elucidated.Key words: ageing, oxidative stress, vascular reactivity.

2011 ◽  
Vol 300 (4) ◽  
pp. R1001-R1008 ◽  
Author(s):  
Robert L. Thunhorst ◽  
Connie L. Grobe ◽  
Terry G. Beltz ◽  
Alan Kim Johnson

These experiments examined water-drinking and arterial blood pressure responses to β-adrenergic receptor activation in young (4 mo), “middle-aged” adult (12 mo), and old (29 mo) male rats of the Brown-Norway strain. We used isoproterenol to simultaneously activate β1- and β2-adrenergic receptors, salbutamol to selectively activate β2-adrenergic receptors, and the combination of isoproterenol and the β2-adrenergic receptor antagonist ICI 118,551 to stimulate only β1-adrenergic receptors. Animals received one of the drug treatments, and water drinking was measured for 90 min. About 1 wk later, animals received the same drug treatment for measurement of arterial blood pressure responses for 90 min. In some rats, levels of renin and aldosterone secretion in response to isoproterenol or salbutamol were measured in additional tests. Old and middle-aged rats drank significantly less after isoproterenol than did young rats and also had greater reductions in arterial blood pressure. Old and middle-aged rats drank significantly less after salbutamol than did young rats, although reductions in arterial blood pressure were equivalent across the ages. The β2-adrenergic antagonist ICI 118,551 abolished drinking after isoproterenol and prevented most of the observed hypotension. Renin secretion after isoproterenol and salbutamol was greater in young rats than in middle-aged rats, and wholly absent in old rats. Aldosterone secretion was reduced in old rats compared with young and middle-aged rats after treatment with isoproterenol, but not after treatment with salbutamol. In conclusion, there are age-related differences in β-adrenergic receptor-mediated drinking that can be explained only in part by age-related differences in renin secretion after β-adrenergic receptor stimulation.


2010 ◽  
Vol 299 (5) ◽  
pp. R1135-R1141 ◽  
Author(s):  
Robert L. Thunhorst ◽  
Terry G. Beltz ◽  
Alan Kim Johnson

We investigated water drinking and arterial blood pressure responses to intravenous infusions of ANG II in young (4 mo), middle-aged adult (12 mo), and old (29 mo) male Brown Norway rats. Infusions of ANG II began with arterial blood pressure either at control levels or at reduced levels following injection of the vasodilator minoxidil. Under control conditions, mean arterial pressure (MAP) in response to ANG II rose to the same level for all groups, and middle-aged and old rats drank as much or more water in response to ANG II compared with young rats, depending on whether intakes were analyzed using absolute or body weight-adjusted values. When arterial blood pressure first was reduced with minoxidil, MAP in response to ANG II stabilized at significantly lower levels compared with control conditions for all groups. Young rats drank significantly more water under reduced pressure conditions compared with control conditions, while middle-aged and old rats did not. Urine volume in response to ANG II was lower, while water balance was higher, under conditions of reduced pressure compared with control conditions. Baroreflex control of heart rate was substantially reduced in old rats compared with young and middle-aged animals. In summary, young rats appear to be more sensitive to the inhibitory effects of increased arterial blood pressure on water drinking than are older animals.


2020 ◽  
Vol 2020 ◽  
pp. 1-9 ◽  
Author(s):  
Naphatsanan Duansak ◽  
Pritsana Piyabhan ◽  
Umarat Srisawat ◽  
Jarinyaporn Naowaboot ◽  
Nusiri Lerdvuthisopon ◽  
...  

Background. Inflammation and hypertension are primary mechanisms involving in obesity-associated adverse effects of a high-fat diet. The aim of this study was to evaluate the effects of rice bran extract (RBE) on arterial blood pressure, hepatic steatosis, inflammation, and oxidative stress in high-fat diet (HFD)-induced obese mice. Methods. Male ICR mice were divided into four groups, including a normal-diet control group, a high-fat diet (HFD) (60% kcal from fat) group, an HFD group treated with RBE (220 mg/kg/day), and an HFD group treated with 1100 mg/kg/day for eight weeks. Besides body weight and arterial blood pressure, we determined liver values of total cholesterol, triglyceride, as well as percent body fat, tumor necrosis factor-α (TNF-α), malondialdehyde (MDA), nuclear factor kappa-B (NF-κB), matrix metalloprotease-9 (MMP-9), cyclooxygenase-2 (COX-2), and mRNA endothelial nitric oxide synthase (eNOS). Results. The HFD group had increased body weight, increased systolic and diastolic blood pressure, liver total cholesterol, triglyceride, NF-κB, COX-2 and MMP-9 protein levels, and decreased mRNA eNOS in the aorta. Mice of the HFD group receiving RBE had reduced diastolic blood pressure, as well as significantly decreased liver and serum TNF-α and MDA levels in the liver, and reduced NF-κB levels in both the liver and heart. Conclusions. These results demonstrate that RBE decreases diastolic blood pressure, the liver lipid droplet accumulation, liver and myocardial NF-κB, myocardial COX-2 and MMP-9 protein levels, and oxidative stress. Moreover, RBE may improve endothelial function and may alleviate adverse health effects associated with obesity including obesity-associated hypertension.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
A B Chaker ◽  
P Algara-Suarez ◽  
L Remila ◽  
C Bruckert ◽  
S H Park ◽  
...  

Abstract Introduction Ageing is characterized by endothelial dysfunction and vascular oxidative stress affecting initially arterial sites at risk. Anthocyanin-rich products are potent stimulators of the endothelial formation of nitric oxide. Sodium-glucose co-transporter 1 (SGLT1) expression has been shown to be increased by oxidative stress and mediate anthocyanin uptake in endothelial cells. Purpose The study determined whether ageing is associated with an upregulation of SGLT1 in arterio-susceptible (aortic arch) and resistant (aorta) sites, and evaluated the vascular SGLT1-mediated anthocyanin uptake. In addition, the impact of a 2-week ingestion of an anthocyanin-rich blackcurrant concentrate (ARBC) by old rats on vascular anthocyanin uptake and oxidative stress, and systolic blood pressure (SBP) was assessed. Methods Male Wistar rats (22-month old) were either untreated or treated with ARBC (60 and 120 mg/kg/day) in the drinking water for 2 weeks. SGLT1 expression was assessed by immunofluorescence, anthocyanin accumulation by Neu A reagent using a purified extract (BCE) prepared from ARBC, oxidative stress by dihydroethidium using confocal microscopy, and SBP by tail-cuff sphingomanometry. Results SGLT1 immunofluorescence was observed predominantly in the endothelium and was higher in the aortic arch than the aorta in old rats whereas only low levels were observed in young rats (12-week old). Exposure of vascular sections to BCE resulted in anthocyanin uptake exclusively in the endothelium, which was higher in the aortic arch than the aorta, and more pronounced in old than young rats. Anthocyanin uptake induced by BCE in the aorta was markedly reduced by LX4211 (a SGLT1/2 inhibitor) both in old and young rats. A high level of oxidative stress was observed throughout the aortic wall of old compared to young rats, which was inhibited by LX4211. Ingestion of ARBC by old rats resulted in a dose-dependent accumulation of anthocyanins throughout the aorta wall and the aortic arch. The tissue accumulation of anthocyanins was associated with a reduced level of oxidative stress. Ageing was associated with increased SBP by about 8 mmHg, which was reduced by ARBC 60 and 120 mg/kg/day treatment by about 5 and 7 mmHg, respectively. Conclusion The present findings indicate that ageing is associated with an upregulation of SGLT1 predominantly in the endothelium and that this effect is more pronounced at the aortic arch than the aorta. The increased endothelial expression level of SGLT1 promoted a greater accumulation of anthocyanins sensitive to LX4211. In addition, a 2-week ingestion of ARBC by old rats resulted in the accumulation of anthocyanins throughout the arterial wall of the aortic arch and aorta, and resulted in a reduced level of oxidative stress and systolic blood pressure. Thus, SGLT1 may be an attractive target to restore vascular protection at arterial sites at risk by promoting endothelial and vascular uptake of anthocyanins.


2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Fidèle Ntchapda ◽  
Christian Bonabe ◽  
Albert Donatien Atsamo ◽  
David Romain Kemeta Azambou ◽  
Yannick Bekono Fouda ◽  
...  

Background. Adansonia digitata is a plant used against cardiovascular disorders in African folk medicine. We assessed the effects of the aqueous extract of its stem bark on the development of hypertension in L-NAME-induced hypertensive rats. Methods. The animals were administered L-NAME once daily for 3 weeks (25 mg/kg, i.p.), concomitantly with aqueous extract of A. digitata stem bark (100 and 200 mg/kg, p.o.) or captopril (20 mg/kg, p.o.). Then, hemodynamic and electrocardiographic parameters, oxidative stress markers, and the lipid profile were assessed in the blood and heart, aorta, and kidney homogenates, and histopathological analyses were performed. Results. L-NAME-induced hypertensive control animals, but not the animals concomitantly treated with A. digitata extract, displayed increases in the mean arterial blood pressure (21.64% difference, p<0.001, vs. dose 200 mg/kg), systolic arterial blood pressure (21.33%, p<0.001), and the diastolic arterial blood pressure (21.84%, p<0.001). In addition, hypertensive control animals displayed (i) increases in serum triglycerides, total cholesterol, LDL, and creatinine levels, malondialdehyde and transaminase activities, and atherogenic index; (ii) decreases in serum HDL, catalase, reduced glutathione, and nitric oxide; and (iii) aorta wall thickening, inflammatory cell infiltration, and cell loss in the cardiac muscle and renal tissues. As captopril, the extract prevented hypertension-like changes in lipid profile, cardiac, hepatic, and renal affection indicators, and oxidative stress markers. Conclusion. Our findings suggest that the extract of A. digitata has antihypertensive and antioxidant effects in L-NAME-induced hypertension rat models. These effects partly justify the traditional medicine use against cardiovascular disorders.


Perfusion ◽  
2014 ◽  
Vol 30 (3) ◽  
pp. 233-238 ◽  
Author(s):  
A Momin ◽  
MTA Sharabiani ◽  
O Wendler ◽  
GD Angelini ◽  
J Desai

1996 ◽  
Vol 271 (6) ◽  
pp. H2368-H2376 ◽  
Author(s):  
D. D. Ku ◽  
L. Guo ◽  
J. Dai ◽  
C. G. Acuff ◽  
M. E. Steinhelper

Recent advances in genetic methods permit the introduction of random and defined mutations into the mouse germ line, producing novel mouse strains, some of which affect the heart and vasculature. A TTR-ANF transgenic strain of mice, which constitutively expresses a fusion gene consisting of the transthyretin promoter and the ANF structural gene, has been shown to result in a lifelong elevation of plasma atrial natriuretic factor (ANF) and a chronically lowered arterial blood pressure. However, no established method for efficient functional analysis of possible alterations in coronary vascular function in mice has been reported. In the present study, we describe an isolated mouse coronary artery preparation that permits an effective and reproducible evaluation of coronary endothelial and vascular function. Both left main and right coronary arteries (resting luminal diam 70-90 microns) were isolated and pressurized, and changes in luminal diameter were determined by videomicroscopy. The coronary pressure-luminal diameter relationship was not significantly different between TTR-ANF transgenic and nontransgenic littermates. Relaxation of coronaries to 0.1-100 nM ANF was significantly reduced in transgenic [maximum effect (Emax) = 43 +/- 10% (mean +/- SE) of 11 vessels] compared with nontransgenic (Emax = 73 +/- 7%, n = 15) mice. Similarly, the relaxant response to an endothelium-dependent dilator, acetylcholine, but not to endothelium-independent dilators sodium nitroprusside and isoproterenol, was significantly decreased in transgenic (Emax = 46 +/- 10%, n = 12) compared with nontransgenic (Emax = 85 +/- 5%, n = 14) mice. In contrast, the dose-dependent vasoconstriction to endothelin-1, KCl and the thromboxane mimetic U-46619 was not significantly different between the two groups. These results indicate that lifelong ANF elevation in mice is associated with a decreased responsiveness of coronary vasorelaxation to ANF, possibly resulting from receptor downregulation and/or desensitization. Endothelium-dependent relaxation was also significantly depressed in transgenic mouse coronary arteries, but smooth muscle-specific dilation and constriction were not affected. The present findings are consistent with previous studies of TTR-ANF transgenic mice showing that ANF regulates arterial blood pressure and vascular function.


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