Chronic Mild Hyperhomocysteinemia Induces Aortic Endothelial Dysfunction but Does Not Elevate Arterial Pressure in Rats

Villeneuve, Nicole; Brunel-Jacquemin, C; Petit, Christine; Guillaumin, Jean-Philippe; Gransagne, Denis; Briant, Cyril; Vilaine, Jean‐Paul; Vanhoutte, Paul M.

doi:10.1159/000083972

Cited by 12 publications

(15 citation statements)

References 73 publications

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“…Consequently, the present results may better represent vasodilator efficiency. In addition, in previous studies the HHcys‐related increases in arterial stiffness and the reduction in vasodilator responses to ACh and NO 10,23,37,43,44 were observed under chronic conditions, whereas rats in the present study were treated with DL‐HT for 15 days. Owing to the short treatment period, it is possible that vascular changes and endothelium dysfunction were not yet established, suggesting activation of compensatory mechanisms opposing increased baseline MAP at early stages of HHcys.…”

Section: Discussionmentioning

confidence: 42%

“…The hypothesis that HHcys may increase blood pressure can be tested experimentally by feeding dl ‐homocysteine thiolactone (DL‐HT) to laboratory animals and studying its cardiovascular effects. Hyperhomocysteinaemia is assumed when the homocysteine concentration is higher than 12 µmol/L, being divided approximately into mild (< 30 µmol/L), moderate (30–100 µmol/L) or severe (> 100 µmol/L) HHcys 21–23 …”

Section: Introductionmentioning

confidence: 99%

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Hyperhomocysteinaemia‐induced Cardiovascular Changes in Rats

Resstel¹,

Andrade²,

Haddad

et al. 2008

Clin Exp Pharma Physio

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(1) Increased plasma homocysteine content and increased blood pressure are independently associated with higher cardiovascular risks. The present study was designed to determine the effects of hyperhomocysteinaemia (HHcys) on the activity of the cardiovascular system in rats. (2) Using male Wistar rats, the effect of moderate HHcys, induced by treating rats with dl-homocysteine thiolactone (DL-HT; 1 g/kg per day) for 15 days, on arterial blood pressure, heart rate, baroreflex and vascular reactivity was determined. (3) Hyperhomocysteinaemia was observed after 15 days of treatment. Baseline arterial blood pressure and heart rate values of HHcys animals were significantly increased after 15 days of treatment. Plasma homocysteine and cardiovascular parameters returned to control values after termination of treatment. Baroreflex gain was significantly enhanced in HHcys rats. The pressor effect of an i.v. infusion of phenylephrine (50 mg/kg per mL) was decreased in HHcys rats and returned to control values after washout of DL-HT. Hypotensive responses to i.v. infusions of sodium nitroprusside (70 mg/kg per mL) or acetylcholine (10 mg/kg per mL) were increased in HHcys animals and returned to control values after washout of DL-HT. The increase in resting arterial blood pressure associated with the moderate HHcys was reversed by treatment with the b1-adrenoceptor antagonist atenolol, suggesting that HHcys-related hypertension is related to increase in cardiac sympathetic activity. (4) The present study showed significantly increased arterial blood pressure, heart rate and baroreflex activity in the early phase of moderate HHcys. In addition, HHcys was associated with alterations of vascular responsiveness to pressor and depressor agents, as well as increased cardiac sympathetic activity. The fact that cardiovascular changes observed in HHcys were reversed after DL-HT washout indicate that moderate HHcys evokes cardiovascular changes.

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Section: Discussionmentioning

confidence: 42%

Section: Introductionmentioning

confidence: 99%

Hyperhomocysteinaemia‐induced Cardiovascular Changes in Rats

Resstel¹,

Andrade²,

Haddad

et al. 2008

Clin Exp Pharma Physio

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“…(a) Astragaloside IV-induced relaxation was observed in endothelium-intact (᭹) and -denuded (᭺) rat aortic rings. The relaxation responses by astragaloside IV were tested on intact rat aortic rings precontracted with phenylephrine in the presence of (b) control (᭺), N w -nitrol-arginine methyl ester (l-NAME) (᭛), 1H [1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (᭡), indomethacin (), and l-NAME + indomethacin (᭹); and (c) control (᭺), 7-nitroindazole (᭡), and N w -nitro-l-arginine (). The rings were pre-incubated with these drugs for 15 min before phenylephrine was added.…”

Section: Discussionmentioning

confidence: 99%

“…To investigate possible mechanisms responsible for astragaloside IV-induced relaxation, the preparations with endothelium were contracted with phenylephrine (1 mmol/L) 30 min after being incubated with one of the following drugs: N w -nitro-l-arginine methyl ester (l-NAME; 100 mmol/L), 1H [1,2,4] oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; 10 mmol/L), indomethacin (10 mmol/L), 7-nitroindazole (100 mmol/L), or N w -nitro-l-arginine (l-NNA; 100 mmol/L).…”

Section: Experimental Protocolsmentioning

confidence: 99%

Mechanisms Underlying Vasorelaxant Action of Astragaloside Iv in Isolated Rat Aortic Rings

Zhang

Wang

Zhong

et al. 2007

Clin Exp Pharma Physio

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1. Astragaloside IV is a component from the widely used traditional Chinese herb Astragalus membranaceus and its effect on rat aortic ring contraction and relaxation were investigated. 2. The aorta from male Sprague-Dawley rats was isolated in an organ bath and ring tension was recorded with or without endothelium. Cumulative effects of astragaloside IV on vessel contraction and relaxation were observed in the presence of various antagonists related to vessel activity. 3. Astragaloside IV showed concentration-dependent inhibition of vessel contraction induced by phenylephrine and potassium chloride. The amount of calcium released from intracellular stores sensitive to phenylephrine was also markedly reduced by astragaloside IV. There was dose-dependent vasorelaxation in endothelium-intact rings, which was partly inhibited by pre-incubation with nitric oxide (NO) synthase (NOS) Nomega-nitro-L-arginine methyl ester and guanylate cyclase inhibitor, 1H-[1,2,4] oxadiazolo [4,3-alpha] quinoxalin-1-one. Astragaloside IV also induced a significant increase in aortic tissue content of guanosine 3",5"-cyclic monophosphate (cGMP) both in vivo and in vitro. Endothelial NOS inhibitor Nomega-nitro-L-arginine prevented vasodilatation, whereas neuronal NOS inhibitor 7-nitroindazole did not show significant influence on the vessel relaxation of astragaloside IV. 4. In conclusion, astragaloside IV inhibited vessel contraction through blocking calcium influx and intracellular calcium release. The endothelium-dependent vessel dilation of astragaloside IV was attributed mainly to the endothelium-dependent NO-cGMP pathway.

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“…It has been reported previously that heterozygous CBS deficient mice presented endothelial dysfunction [36,37], but in our experiments we could not detect any blood pressure changes that might be related to the reported endothelial dysfunction of these animals. In this regard, endothelial dysfunction with mild hyperhomocysteinemia has been demonstrated in a large number of animal models and humans [38], but this Low HDL and hyperhomocysteinemia Carnicer et al 1601 impairment, likely due to increased oxidative stress and impaired nitric oxide bioactivity, was not translated into higher blood pressure levels [39]. Our results suggest that mild homocysteinemia requires an additional factor to be translated into clinical hypertension, and this is the decrease in the APOA-I-containing particles of HDL.…”

Section: Discussionmentioning

confidence: 99%