Biomedical subjects

Ramaroson Andriantsitohaina

Publications and source records attributed to Ramaroson Andriantsitohaina.

At least 19 recordsLinked to original sources

PubMed2006

Fenofibrate improves age-related endothelial dysfunction in rat resistance arteries.

This study was designed to test the hypothesis that fenofibrate, the peroxisome proliferator-activated receptor alpha (PPARalpha) activator, improves age-related endothelial dysfunction in small mesenteric arteries (SMA). Adult and aged rats were treated with fenofibrate and then endothelium-dependent relaxations of SMA; expressions of endothelial NO synthase (eNOS), cyclo-oxygenase (COX-1 and COX-2) and superoxide dismutases (SOD) (Cu/Zn SOD, Mn SOD and EC SOD) proteins and release of TXB(2) and 6-keto-PGF(1alpha) were assessed. Fenofibrate improved endothelium-dependent vasodilatation of arteries from old rats and decreased participation of endothelial vasoconstrictor products, sensitive to COX-1 and COX-2 inhibitors and acting on Tp receptor. Fenofibrate decreased expressions of COX-1 and COX-2, and generation of TXA(2). Release of vasodilator PGI(2) and U46619-induced contraction remained unaltered. Neither NO-mediated vasodilatation nor eNOS expression was affected. The addition of the scavengers, SOD and catalase increased relaxation only in SMA from control rats. Finally, fenofibrate did not change expressions of Cu/Zn SOD and Mn SOD but it increased EC SOD towards that observed in arteries from adult rats. Fenofibrate improves endothelial function in resistance arteries from aged rats by decreasing expression of COX-1 and COX-2 together with enhancing anti-oxidant capacity of the vessel wall probably through the increased expression of EC SOD. This study provides evidence that PPARalpha may have clinical applications toward maintaining endothelial function during ageing.

Aging↗

PubMed2006

Protective role of polyphenols in cyclosporine A-induced nephrotoxicity during rat pregnancy.

The aim of this study was to evaluate the adverse effects of cyclosporine A (CsA) toward renal morphogenesis and to test the renoprotective natural antioxidants such as provinol (PV). Pregnant rats were divided into four groups. Group I was injected SC with olive oil. Group II was treated with oral administration of PV and was used as control. Group III animals were injected SC daily with CsA, and group IV animals were injected daily with CsA and PV for 21 days of pregnancy. Five pups per litter were killed and the kidneys removed and treated by morphological and immunohistochemical (IHC) methods. IHC analysis considered two proteins responsible for nephrotoxicity in adult rats: inducible nitric oxide (iNOS) and matrix metalloproteinase-2 (MMP2). Pregnancy outcomes among CsA-treated rats demonstrated a reduced number of pups. Pups that were exposed antenatally to CsA presented several pathologic findings in all immature parenchyma and an increase in iNOS and MMP2 expression. These side effects were not observed in kidney of litters born from CsA + PV-treated mothers. Our study indicates that CsA induces morphological alterations in renal parenchyma of neonates and that PV plays a protective role against these side effects.

Animals↗

PubMed2006

Deletion of peroxisome proliferator-activated receptor-alpha induces an alteration of cardiac functions.

The peroxisome proliferator-activated receptor-alpha (PPARalpha) plays a major role in the control of cardiac energy metabolism. The role of PPARalpha on cardiac functions was evaluated by using PPARalpha knockout (PPARalpha -/-) mice. Hemodynamic parameters by sphygmomanometric measurements show that deletion of PPARalpha did not affect systolic blood pressure and heart rate. Echocardiographic measurements demonstrated reduced systolic performance as shown by the decrease of left ventricular fractional shortening in PPARalpha -/- mice. Telemetric electrocardiography revealed neither atrio- nor intraventricular conduction defects in PPARalpha -/- mice. Also, heart rate, P-wave duration and amplitude, and QT interval were not affected. However, the amplitude of T wave from PPARalpha -/- mice was lower compared with wild-type (PPARalpha +/+) mice. When the myocardial function was measured by ex vivo Langendorff's heart preparation, basal and beta-adrenergic agonist-induced developed forces were significantly reduced in PPARalpha-null mice. In addition, Western blot analysis shows that the protein expression of beta1-adrenergic receptor is reduced in hearts from PPARalpha -/- mice. Histological analysis showed that hearts from PPARalpha -/- but not PPARalpha +/+ mice displayed myocardial fibrosis. These results suggest that PPARalpha-null mice have an alteration of cardiac contractile performance under basal and under stimulation of beta1-adrenergic receptors. These effects are associated with myocardial fibrosis. The data shed light on the role of PPARalpha in maintaining cardiac functions.

Adaptation, Physiological↗

PubMed2006

Endothelial function and cardiovascular disease: effects of quercetin and wine polyphenols.

Endothelial dysfunction is an early pathophysiological feature and independent predictor of poor prognosis in most forms of cardiovascular diseases. Epidemiological studies report an inverse association between dietary flavonoid consumption and mortality from cardiovascular diseases. In the present paper, we review the effects of flavonoids, especially quercetin and wine polyphenols, on endothelial function and dysfunction and its potential protective role in hypertension, ischemic heart disease and stroke. In vitro studies show that flavonoids may exert multiple actions on the NO-guanylyl cyclase pathway, endothelium-derived hyperpolarizing factor(s) and endothelin-1 and protect endothelial cells against apoptosis. In vivo, flavonoids prevent endothelial dysfunction and reduce blood pressure, oxidative stress and end-organ damage in hypertensive animals. Moreover, some clinical studies have shown that flavonoid-rich foods can improve endothelial function in patients with hypertension and ischemic heart disease. Altogether, the available evidence indicates that quercetin and wine polyphenols might be of therapeutic benefit in cardiovascular diseases even though prospective controlled clinical studies are still lacking.

Cardiovascular Diseases↗

PubMed2006

Shed membrane particles from preeclamptic women generate vascular wall inflammation and blunt vascular contractility.

We investigated the role of microparticles in vascular dysfunction of the multisystemic disorder of preeclampsia in women's omental arteries or mouse arteries. Preeclamptic women displayed increased circulating levels of leukocyte- and platelet-derived microparticles compared with healthy pregnant individuals. Microparticles from preeclamptic, but not healthy, pregnant women induced ex vivo vascular hyporeactivity to serotonin in human omental arteries and mouse aortas. Hyporeactivity was reversed by a nitric-oxide (NO) synthase inhibitor and associated with increased NO production. In the presence of a cyclooxygenase (COX)-2 inhibitor, serotonin-mediated contraction was partially reduced in arteries treated with healthy microparticles but was abolished after treatment with preeclamptic microparticles. This was associated with increased 8-isoprostane production. Preeclamptic microparticles induced up-regulation of inducible nitric-oxide synthase and COX-2 expression, evoked nuclear factor-kappaB activation, and enhanced oxidative and nitrosative stress. Interestingly, the microparticles originating most probably from leukocytes were responsible for the COX-2 vasoconstrictor component of preeclamptic microparticles, whereas those of platelet origin were mainly involved in NO release. Moreover, vascular hyporeactivity was observed in arteries taken from mice treated in vivo with preeclamptic microparticles. This study demonstrates pathophysiological relevance and provides a paradoxical effect of preeclamptic microparticles associated with proinflammatory properties on vessels, leading to enhanced NO and superoxide anion levels and counteraction of increased COX-2 metabolites.

Animals↗

PubMed2005

Upregulation of proinflammatory proteins through NF-kappaB pathway by shed membrane microparticles results in vascular hyporeactivity.

OBJECTIVE: Microparticles are membrane vesicles with procoagulant and proinflammatory properties released during cell activation, including apoptosis. The present study was designed in dissecting the effects evoked by microparticles on vascular reactivity. METHODS AND RESULTS: Microparticles from either apoptotic T lymphocytic cells or from plasma of diabetic patients with vascular complications induced vascular hyporeactivity in response to vasoconstrictor agents in mouse aorta. Hyporeactivity was reversed by nitric oxide (NO) synthase plus cyclooxygenase-2 inhibitors, and associated with an increased production of vasodilatory products such as NO and prostacyclin. Microparticles induced an upregulation of proinflammatory protein expressions, inducible NO-synthase and cyclooxygenase-2, mainly in the medial layer of the vessels as evidenced by immunochemical staining. In addition, microparticles evoke NF-kappaB activation probably through the interaction with the Fas/Fas Ligand pathway. Finally, in vivo treatment of mice with lymphocyte-derived MPs induces vascular hyporeactivity, which was reversed by the combination of NO and cyclooxygenase-2 inhibitors. CONCLUSIONS: These data provide a rationale to explain the paracrine role of microparticles as vectors of transcellular exchange of message in promoting vascular dysfunction during inflammatory diseases.

6-Ketoprostaglandin F1 alpha↗

PubMed2005

Deletion of MLCK210 induces subtle changes in vascular reactivity but does not affect cardiac function.

Myosin light chain kinase (MLCK) plays a key role in the regulation of actomyosin contraction in a large variety of cells. Two isoforms have been described: a short isoform, widely expressed in smooth muscle cells; and a long isoform (MLCK210), mainly localized in the endothelium. This study investigated the consequences on different cardiovascular parameters of MLCK210 gene deletion using MLCK210 knockout mice and of pharmacological inhibition of the kinase using a specific MLCK inhibitor. Deletion of MLCK210 did not affect systolic blood pressure and heart rate or echocardiographic measurements. Electrocardiographic analysis showed neither atrio- nor intraventricular conduction or repolarization defects. Ex vivo responses of aortic rings to vasoconstrictor and vasodilator agonists were not modified in MLCK210 null mice. However, deletion of MLCK210 attenuated shear stress-induced dilation and produced changes in the balance of endothelial-relaxing factors of small mesenteric arteries (SMA). In particular, a reduced flow-mediated NO-dependent dilation was observed. However, it was partially compensated by enhanced indomethacin-sensitive dilation. No significant changes were detected in the endothelium-derived hyperpolarizing component of the vasodilator response. The above effects of MLCK210 gene deletion were confirmed in SMA from wild-type mice by the use of the MLCK enzymatic inhibitor MMZ-10-057. In summary, deletion of MLCK210 was not associated with abnormalities of main in vivo cardiovascular parameters in mice. This study demonstrates a role for MLCK210 in the regulation of flow-dependent dilation in SMA.

Animals↗

PubMed2005

Provinol prevents CsA-induced nephrotoxicity by reducing reactive oxygen species, iNOS, and NF-kB expression.

Cyclosporine A (CsA) use is associated with several side effects, the most important of which is nephrotoxicity that includes, as we previously showed, tubular injury and interstitial fibrosis. Recently, many researchers have been interested in minimizing these effects by pharmacological interventions. To do this, we tested whether the administration of a red wine polyphenol, Provinol (PV), prevents the development of CsA-induced nephrotoxicity. Rats were treated for 21 days and divided into four groups: control; group treated with PV (40 mg/kg/day by oral administration in tap water); group treated with CsA (15 mg/kg/day by subcutaneous injection); group treated with CsA plus PV. CsA produced a significant increase of systolic blood pressure; it did not affect urinary output, but caused a significant decrease in creatinine clearance. These side effects were associated with an increase in conjugated dienes, which are lipid peroxidation products, inducible NO-synthase (iNOS), and nuclear factor (NF)-kB, which are involved in antioxidant damage. However, PV prevented these negative effects through a protective mechanism that involved reduction of both oxidative stress and increased iNOS and NF-kB expression induced by CsA. These results provide a pharmacological basis for the beneficial effects of plant-derived polyphenols against CsA-induced renal damage associated with CsA.

Animals↗

PubMed2005

Improvement of age-related endothelial dysfunction by simvastatin: effect on NO and COX pathways.

The effects of oral administration of the HMG-CoA reductase inhibitor, simvastatin (SV), on age-related endothelial dysfunction were investigated in the aorta of male Wistar rats. Adult (12-14 weeks) and old (60-80 weeks) rats were treated daily for 12 weeks with either vehicle or SV (1 mg kg(-1)). In old rats, SV treatment did not significantly affect systolic blood pressure and LDL-cholesterol, but it reduced plasma cholesterol, triglycerides and oxidised LDL though it did not affect total antioxidant status. SV improved endothelium-dependent relaxation to acetylcholine and A-23187 in vessels from aged, but not adult, rats. This effect was linked to a greater NO vasodilatation via an increased expression of endothelial NO-synthase. A mechanism sensitive to superoxide dismutase and catalase also accounts for enhanced endothelial vasodilatation. Finally, SV did not affect the release of prostacyclin, but it inhibited the generation of thromboxane (TX) A2 from COX-2 isoform. The effect of the latter was sensitive to the Tp receptor antagonist, ICI-192,605. The present study provides evidence that oral administration of SV improves endothelial dysfunction in the aorta from aged rats by mechanisms associated with enhanced NO vasodilatation, reduced release of TXA2 from cyclo-oxygenase, and increased antioxidant properties of the vessel wall. These data underscore a new therapeutic perspective for SV in age-related endothelial dysfunction.

Acetylcholine↗

PubMed2005

Shed membrane microparticles from circulating and vascular cells in regulating vascular function.

Inflammation has a pivotal role in the development of atherosclerosis and acute activation of the vascular wall with consecutive local thrombosis and altered vasomotion. This process is orchestrated by the interactions between inflammatory cells, such as platelets and T and B lymphocytes, and vascular cells, endothelial cells, and smooth muscle cells. When they are activated by an agonist, shear stress, or apoptosis, these cells release vesicles shed from the blebbing plasma membrane called microparticles. Microparticles harbor cell surface proteins and contain cytoplasmic components of the original cell. They exhibit negatively charged phospholipids, chiefly phosphatidylserine, at their surface, which accounts for their procoagulant character and proinflammatory properties, including alteration of vascular function. Elevated levels of circulating microparticles have been detected in pathological states associated with vascular dysfunction, including attenuation of endothelium-dependent vasodilatation and/or alteration of responsiveness of vascular smooth muscle to vasoconstrictor stimuli in conductance and resistance arteries. This review points out the characteristics of microparticles as well as the biological messages they can mediate. In particular, it summarizes the signaling cascades involved in microparticle-induced vascular dysfunction with special attention to the cellular origin of these vesicles (platelet, endothelial, and leukocytic), which may explain their differential consequences on vascular remodeling. The available information provides a rationale for the paracrine role of microparticles as vectors of transcellular exchange of message between circulating cells and cells from the vascular wall.

Animals↗

PubMed2005

Polyphenols as potential therapeutical agents against cardiovascular diseases.

Increasing evidence suggests that polyphenols from fruits, vegetables and beverages such as wine and tea may exert protective effects on the cardiovascular system. Indeed, research in the field of polyphenols points out their antioxidant and free radical scavenging properties, leading to lower low-density lipoprotein (LDL) oxidation and platelet aggregation. These compounds are also able to modulate the generation of nitric oxide (NO) from vascular endothelium and to interfere with the mechanisms leading to inflammation and endothelial apoptosis, contributing to the prevention of the endothelial dysfunction, known to play a central role in the pathogenesis of cardiovascular diseases. This article reviews the potential targets of polyphenols involved in the complex pathophysiological events occurring in cardiovascular diseases, such as hypertension, atherosclerosis and stroke.

Animals↗

PubMed2004

Wine polyphenols induce hypotension, and decrease cardiac reactivity and infarct size in rats: involvement of nitric oxide.

1. The effects of short-term oral administration of red wine polyphenolic compounds (RWPC, 20 mg x kg(-1) day(-1) for 7 days) on haemodynamics, ex vivo cardiac responsiveness and ischaemia-reperfusion injury were investigated in rats. The involvement of nitric oxide (NO) was evaluated using the NO synthase inhibitor, N(G)-nitro-l-arginine methyl ester (l-NAME, 2 mg x kg(-1) day(-1) for 7 days), at a dose which did not affect blood pressure. 2. Ex vivo reactivity of hearts from RWPC-treated rats showed lower basal developed pressure, greater heart rate and decreased inotropic responses to either beta-adrenoceptor or muscarinic receptor stimulation with isoprenaline or carbachol, respectively.3. RWPC treatment did not modify cardiac expression of endothelial NO synthase or Cu/Zn superoxide dismutase. However, it increased nitrite in the coronary effluent. 4. In ischaemia-reperfusion, RWPC treatment reduced infarct size and oxidative stress, as shown by the myocardial content of the end products of lipid peroxidation, malondialdehyde and 4-hydroxynonenal, without affecting post-ischaemic contractile dysfunction. All the observed effects of RWPC were prevented by l-NAME treatment. 5. Altogether, these data show that short-term treatment with RWPC decreases blood pressure and cardiac responsiveness, and protects against post-ischaemic infarction via decreased oxidative stress. All the above effects of RWPC are sensitive to NO synthase inhibition that implies an involvement of NO-dependent pathway. This study suggests a basis for the beneficial effects of plant-derived polyphenols against cardiovascular disease.

Administration, Oral↗

PubMed2004

Shed membrane particles from T lymphocytes impair endothelial function and regulate endothelial protein expression.

BACKGROUND: Microparticles (MPs) are membrane vesicles with procoagulant and proinflammatory properties released during cell activation. The present study was designed to dissect the effects evoked by T lymphocyte-derived MPs on vascular function. METHODS AND RESULTS: MPs were produced by treatment of the human lymphoid CEM T cell line with actinomycin D or phytohemagglutinin. Incubation of mouse aortic rings with 30 nmol/L MPs resulted in a time-dependent impairment of acetylcholine-induced relaxation of precontracted vessels, with a maximal reduction after 24 hours. MPs also impaired shear stress-induced dilatation of mouse small mesenteric arteries by affecting the nitric oxide (NO) and prostacyclin but not the endothelium-derived hyperpolarizing factor components of the response. However, neither alteration of calcium signaling in response to agonists nor reduction of cyclooxygenase-1 expression accounted for the impairment of the NO and prostacyclin components of the endothelial response. The effect of MPs was rather because of a decrease in expression of endothelial NO synthase and an overexpression of caveolin-1. Furthermore, lymphocyte-derived MPs from diabetic patients or in vivo circulating MPs from either diabetic or HIV-infected patients reduced endothelial NO synthase expression. Finally, the effects of MPs on endothelial cells were not driven through CD11a/CD18 adhesion molecules or the Fas/FasL pathway. CONCLUSIONS: MPs from T cells induce endothelial dysfunction in both conductance and resistance arteries by alteration of NO and prostacyclin pathways. MPs regulate protein expression for endothelial NO synthase and caveolin-1. These data contribute to a better understanding of the deleterious effects of enhanced circulating MPs observed in disorders with cardiovascular or immune complications.

Acetylcholine↗

PubMed2004

Cardiovascular properties of aqueous extract from Mitragyna inermis (wild).

Aqueous extracts of Mitragyna inermis (AEMI) used traditionally as antihypertensive agents produced a concentration-dependent (0.1-3 mg/ml) ex vivo increase in cardiac contractile response and coronary flow but did not modify heart rate in the rat. Interestingly, AEMI produced relaxation in isolated porcine coronary artery at concentration up to 3 mg/ml that was exclusively dependent on the presence of endothelium. This relaxation involved partial depolarization (KCl 20, 40 mM) and NO synthase inhibitor-sensitive mechanisms but was not sensitive to the blockade of cyclo-oxygenase pathway. In contrast, the relaxant effect of AEMI was not dependent on the presence of endothelium in rat tail artery. Taken together, the present study demonstrates hypotensive, cardiotropic and vasodilatory properties of AEMI that contribute to better understanding of its beneficial effect against cardiovascular diseases.

Animals↗

PubMed2004

Red wine polyphenols prevent cardiovascular alterations in L-NAME-induced hypertension.

OBJECTIVE: Red wine polyphenols have been reported to possess beneficial properties for preventing cardiovascular diseases but their effects on hemodynamic and functional cardiovascular changes during inhibition of nitric oxide (NO) synthesis have not been elucidated. DESIGN: The effects of the red wine polyphenols, Provinols, on arterial hypertension as well as left ventricular (LV) hypertrophy, myocardial fibrosis and vascular remodeling were investigated in rats during chronic inhibition of nitric oxide synthase (NOS) activity. Rats were divided into four groups: a control group, a group treated with N-nitro-L-arginine methyl ester (L-NAME) (40 mg/kg per day), a group receiving Provinols (40 mg/kg per day) alone or Provinols plus L-NAME. RESULTS: Provinols markedly reduced the increase in both blood pressure and protein synthesis in the heart and aorta caused by chronic inhibition of NO synthesis. Provinols reduced myocardial fibrosis even though it did not affect LV hypertrophy. In addition, Provinols prevented aortic thickening and corrected the augmented reactivity of the aorta to norepinephrine and the attenuated endothelium-dependent relaxation to acetylcholine in NO-deficient rats. These alterations were associated with an increase of NOS activity, a moderate enhancement of endothelial NOS expression and a reduction of oxidative stress in the LV and aorta. CONCLUSION: Our results provide evidence that Provinols partially prevents L-NAME-induced hypertension, cardiovascular remodeling and vascular dysfunction via the increase of NO-synthase activity and prevention of oxidative stress. Thus, the beneficial effects of plant polyphenols in prevention of hypertension may result from their complex influence on the NO balance in the cardiovascular system.

Alkadienes↗

PubMed2004

Effect of polyphenolic compounds on the renal Na+,K(+)-ATPase during development and persistence of hypertension in rats.

It has been suggested that polyphenolic substances provide protection against the risk factors of cardiovascular diseases. The present study was designed to investigate whether application of red wine polyphenols influences the kinetic properties of the renal Na+,K(+)-ATPase in rats with hypertension (164 +/- 8 mmHg) that was experimentally induced by the NO synthase inhibitor N(G.) -nitro-L- arginine methyl ester (L-NAME). Polyphenols in a dose of 40 mg kg(-1) day(-1) in drinking fluid induced different effects on the properties of the renal Na+,K(+)-ATPase depending on the mode of their administration. Preventive application of polyphenols during the development of hypertension (144 +/- 5 mmHg) partially protected the Na+,K(+)-ATPase molecule against hypertension-induced deterioration via increased capability of the enzyme to bind ATP and/or Na+ as suggested by decrease of Km and KNa, respectively, even to values lower than in controls. However, polyphenols did not prevent the hypertension-induced reduction of the number of active Na+,K(+)-ATPase molecules as shown by similar V(max) values as compared to the hypertensive L-NAME group. The above protection is probably secured by a NO-dependent mechanism as suggested by 150% increase of the NO synthesis. Additional treatment of already hypertensive animals with polyphenols (153 +/- 8 mmHg) resulted in partial restoration of the Na+,K(+)-ATPase affinities especially for sodium as indicated by significant diminution of KNa. However, polyphenols in this mode of application did not slow down the L-NAME-induced decrease in the number of Na+,K(+)-ATPase molecules in the kidney as suggested by additional significant decrease in V(max) values when comparing this group with the control group and also the hypertensive L-NAME group. In this case the polyphenols affected the Na,K-ATPase molecule in a NO-independent way as indicated by the fact that polyphenols failed to restore normal NO synthesis.

Adenosine Triphosphate↗

PubMed2003

Red wine polyphenols cause endothelium-dependent EDHF-mediated relaxations in porcine coronary arteries via a redox-sensitive mechanism.

Moderate consumption of wine is associated with cardiovascular protection most likely by increasing the endothelial formation of nitric oxide (NO). The present study investigated whether red wine polyphenolic compounds (RWPCs) increase the formation of endothelium-derived hyperpolarizing factor (EDHF) in arteries and, if so, to characterize the underlying mechanism. Porcine coronary artery rings were suspended in organ chambers for measurement of changes in isometric tension and membrane potential in the presence of indomethacin and N(omega)-nitro-L-arginine. RWPCs caused pronounced endothelium-dependent relaxations and hyperpolarizations, which were reduced by the combination of charybdotoxin plus apamin (two inhibitors of EDHF-mediated responses). Both responses to RWPCs were also reduced by antioxidants, membrane permeant analogues of superoxide dismutase, and diphenylene iodonium, an inhibitor of flavin-dependent enzymes. RWPCs induced the formation of superoxide in cultured endothelial cells. These findings demonstrate that RWPCs cause EDHF-mediated relaxations of coronary arteries, which are critically dependent on a redox-sensitive mechanism involving a flavin-dependent enzyme.

Animals↗

PubMed2003

Cedrelopsis grevei induced hypotension and improved endothelial vasodilatation through an increase of Cu/Zn SOD protein expression.

This study was designed to investigate the cardiovascular consequences of oral administration of Cedrelopsis grevei (CG) in normotensive rats. Experiments were designed to investigate hemodynamic parameters in vivo as well as the consequences of CG treatment on the vasoconstriction response to norepinephrine and the vasorelaxant response to ACh ex vivo in isolated aortas and small mesenteric arteries (SMA). Treatment of male Wistar rats with 80 mg/kg CG for 4 wk induced a progressive decrease in systolic blood pressure. In the aorta, CG did not significantly alter the response to norepinephrine despite the participation of extraendothelial nitric oxide (NO)-induced hyporeactivity. In the SMA, contraction to norepinephrine was not modified by CG treatment even though it enhanced the participation of endothelial NO. Endothelium-dependent relaxation to ACh was increased in both the aorta and SMA from CG-treated rats. In the aorta from CG-treated rats, the mechanism involved superoxide dismutase (SOD)- and catalase-sensitive free radical production. The latter was associated with enhanced expression of Cu/Zn SOD and endothelial NO synthase. These results suggest that oral administration of CG produces a decrease in blood pressure in normotensive rats. This hemodynamic effect was associated with enhanced endothelium-dependent relaxation and an induction of Cu/Zn SOD and endothelial NO synthase expressions in the vessel wall. They also show subtle mechanisms that compensate for the increased participation of NO to maintain unchanged agonist-induced contractility. These data provide a pharmacological basis for the empirical use of CG against cardiovascular diseases.

Acetylcholine↗