Food Restriction Augmented Alpha1 Adrenergic Mediated Contraction in Mesenteric Arteries

Mapping Intimacies ◽

10.1101/2021.12.12.472277 ◽

2021 ◽

Author(s):

Rany Vorn ◽

Hae Young Yoo

Keyword(s):

Nitric Oxide ◽

Arterial Pressure ◽

Vascular Function ◽

Food Restriction ◽

Vascular Reactivity ◽

Hypovolemic Shock ◽

Mesenteric Arteries ◽

Sprague Dawley ◽

Underlying Mechanisms ◽

Endothelial Nitric Oxide

Food restriction (FR) enhances the sensitivity to cardiopulmonary reflexes and alpha1 adrenoreceptors in the female, despite hypotension. The effect of male FR on cardiopulmonary and systemic vascular function is not well understood. This study examines the effects of FR on cardiopulmonary, isolated mesenteric arterial function and potential underlying mechanisms. We hypothesized that FR decreased eNOS activity in mesenteric arteries. Male Sprague Dawley (SD) rats were randomly divided into three groups: (1) control (n=30), (2) 20 percent of food reduction (FR20, n=30), and (3) 40 percent of food reduction (FR40, n=30) for five weeks. Non-invasive blood pressure was measured twice a week. Pulmonary arterial pressure (PAP) was measured using isolated/perfused lungs in rats. The isolated vascular reactivity was assessed in double-wire myograph. After five weeks, food restricted rats exhibited a lower mean arterial pressure and heart rate, however, only FR40 groups exhibited statistically significant differences. The basal tone of PAP and various vasoconstrictors did not show significant differences in pulmonary circulation between each group. We observed that food restriction were enhanced the sensitivity (EC50) in response to α1-adrenoreceptors (phenylephrine, PhE)-induced vasoconstriction, but not to serotonin, U46619, and high K+ in the mesenteric arteries. FR reduced endothelium-dependent relaxation via decreased function of endothelial nitric oxide synthase (eNOS)-nitric oxide (NO) pathway in the mesenteric arteries. PhE-mediated vasoconstriction in mesenteric arteries was eliminated in the presence of eNOS inhibitor (L-NAME). In addition, incubation with NOX2/4 inhibitors (apocynin, GKT137831, VAS2870) and reactive oxygen species (ROS) scavenger inhibitor (Tiron) were eliminated the differences of PhE-mediated vasoconstriction but not to cyclooxygenase inhibitor (indomethacin) in the mesenteric artery. Augmentation of alpha1 adrenergic mediated contraction via inhibition of eNOS-NO pathway by increased activation of ROS through NOX2/4 in response to FR. Reduced eNOS-NO signaling might be a pathophysiological counterbalance to prevent hypovolemic shock in response to FR.

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Abstract 665: Endothelial Nitric Oxide Negatively Modulates Phenylephrine-induced Contraction In Matrix Metalloproteinase 2 (mmp-2)-filled Rabbit Aortic Rings

Hypertension ◽

10.1161/hyp.60.suppl_1.a665 ◽

2012 ◽

Vol 60 (suppl_1) ◽

Author(s):

Alejandro F Prado ◽

Laena Pernomian ◽

Lusiane M Bendhack ◽

Raquel F Gerlach

Keyword(s):

Nitric Oxide ◽

Matrix Metalloproteinase ◽

Muscle Activity ◽

Vascular Function ◽

Vascular Reactivity ◽

Selective Inhibitor ◽

Matrix Metalloproteinase 2 ◽

Maximum Effect ◽

Endothelial Nitric Oxide

Endothelial nitric oxide negatively modulates Phenylephrine-induced contraction in Matrix metalloproteinase 2 (MMP-2)-filled rabbit aortic rings The present study aimed to evaluate the vascular function of aortic rings after intraluminal injection of matrix metalloproteinase 2 (MMP-2) and contribution of endothelial nitric oxide (NO) in this response. METHODS: thoracic aorta isolated from New Zealand rabbits (3.0 Kg) was isolated and were performed in situ gelatinolytic assay (intraluminal exposure with Krebs solution or MMP-2 1.2 μg/mL, at 37° C for 30 minutes, with measure of fluorescence intensity - FI) or vascular reactivity. Cumulative concentration-effect curves for phenylephrine (PE, 0.1 nM - 10 μM/L) were performed in endothelium-intact (E+) or denuded (E-) aortic rings, in the absence or presence of L-NAME (non-selective inhibitor of NOS, 100 μM) or Hydroxycobalamine (scavenger of intracellular NO), 30 min before the PE curves on E+ rings. The vascular contraction was normalized by grams of tension by dry tissue (g/g) and were analyzed the agonist maximum effect (Emax) and potency (pD2). Data represent mean ± S.E.M and the results were statistically analyzed using Student t test, one-way or two-way ANOVA with Bonferroni pos-hoc (p<0,05). Results: In situ gelatinolytic activity was increased in the vessels filled with MMP-2 (19.19+0.93U,n=5) compared to vehicle (10.75+0.45U,n=5). In the vascular reactivity, E- aortic rings filled with MMP-2 increased Emax of PE (1893,28+122,40g/g,n=9) versus vehicle E- (1485.73+76.82g/g,n=9), but no differences were observed on Emax of E+ aortic rings (vehicle: 1416.13+120.87g/g,n=7; MMP-2: 1893.28+122.40g/g,n=9). The presence of L-NAME induced an increase in Emax of E+ aortic rings filled with vehicle (1817.60+76.37g/g,n=7) or MMP-2 (2340.50+130.43g/g,n=5). Hydroxycobalamine also increased the Emax of E+ aortic rings with vehicle (1889,81+129,17,n=6) or MMP-2 (2480,12+192,57,n=5). No difference of pD2 value was observed in this study. Conclusion: Data suggest this protease cross the aorta layers from the lumen. An increased vasoconstriction in E- vessels suggests a vascular smooth muscle activity of MMP-2. In the presence of L-NAME and Hydroxycobalamine, vessels filled with MMP-2 shows a greater maximum effect suggesting that NO exerts a negative modulation of the PE-induced vasoconstriction on MMP-2 aortic rings.

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Clopidogrel, independent of the vascular P2Y12 receptor, improves arterial function in small mesenteric arteries from AngII-hypertensive rats

Clinical Science ◽

10.1042/cs20090392 ◽

2010 ◽

Vol 118 (7) ◽

pp. 463-471 ◽

Cited By ~ 15

Author(s):

Fernanda R. C. Giachini ◽

David A. Osmond ◽

Shali Zhang ◽

Fernando S. Carneiro ◽

Victor V. Lima ◽

...

Keyword(s):

Nitric Oxide ◽

Vascular Reactivity ◽

Receptor Activation ◽

Mesenteric Arteries ◽

P2y12 Receptor ◽

Sprague Dawley ◽

Pharmacological Characterization ◽

Vascular Responses ◽

Functional Changes ◽

Nitric Oxide Bioavailability

The P2Y12 receptor antagonist clopidogrel blocks platelet aggregation, improves systemic endothelial nitric oxide bioavailability and has anti-inflammatory effects. Since P2Y12 receptors have been identified in the vasculature, we hypothesized that clopidogrel ameliorates AngII (angiotensin II)-induced vascular functional changes by blockade of P2Y12 receptors in the vasculature. Male Sprague–Dawley rats were infused with AngII (60 ng/min) or vehicle for 14 days. The animals were treated with clopidogrel (10 mg·kg−1 of body weight·day−1) or vehicle. Vascular reactivity was evaluated in second-order mesenteric arteries. Clopidogrel treatment did not change systolic blood pressure [(mmHg) control-vehicle, 117±7.1 versus control-clopidogrel, 125±4.2; AngII–vehicle, 197±10.7 versus AngII–clopidogrel, 198±5.2], but it normalized increased phenylephrine-induced vascular contractions [(%KCl) vehicle-treated, 182.2±18% versus clopidogrel, 133±14%), as well as impaired vasodilation to acetylcholine [(%) vehicle-treated, 71.7±2.2 versus clopidogrel, 85.3±2.8) in AngII-treated animals. Vascular expression of P2Y12 receptor was determined by Western blot. Pharmacological characterization of vascular P2Y12 was performed with the P2Y12 agonist 2-MeS-ADP [2-(methylthio) adenosine 5′-trihydrogen diphosphate trisodium]. Although 2-MeS-ADP induced endothelium-dependent relaxation [(Emax %)=71±12%) as well as contractile vascular responses (Emax %=83±12%), these actions are not mediated by P2Y12 receptor activation. 2-MeS-ADP produced similar vascular responses in control and AngII rats. These results indicate potential effects of clopidogrel, such as improvement of hypertension-related vascular functional changes that are not associated with direct actions of clopidogrel in the vasculature, supporting the concept that activated platelets contribute to endothelial dysfunction, possibly via impaired nitric oxide bioavailability.

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Endothelial cell transfusion ameliorates endothelial dysfunction in 5/6 nephrectomized rats

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00132.2013 ◽

2013 ◽

Vol 305 (8) ◽

pp. H1256-H1264 ◽

Cited By ~ 5

Author(s):

Maricica Pacurari ◽

Dongqi Xing ◽

Rob H. P. Hilgers ◽

Yuan Yuan Guo ◽

Zhengqin Yang ◽

...

Keyword(s):

Nitric Oxide ◽

Chronic Kidney Disease ◽

Endothelial Dysfunction ◽

Nitric Oxide Synthase ◽

Kidney Disease ◽

Endothelial Nitric Oxide Synthase ◽

Vascular Function ◽

Vascular Reactivity ◽

Oxide Synthase ◽

Endothelial Nitric Oxide

Endothelial dysfunction is prevalent in chronic kidney disease. This study tested the hypothesis that transfusion of rat aortic endothelial cells (ECs) ameliorates endothelial dysfunction in a rat model of chronic kidney disease. Male Sprague-Dawley rats underwent sham surgery or 5/6 nephrectomy (Nx). Five weeks after Nx, EC (1.5 × 106 cells/rat) or vehicle were transfused intravenously. One week later, vascular reactivity of mesenteric artery was assessed on a wire myograph. Sensitivity of endothelium-dependent relaxation to acetylcholine and maximum vasodilation were impaired by Nx and improved by EC transfusion. Using selective pharmacological nitric oxide synthase isoform inhibitors, we demonstrated that the negative effect of Nx on endothelial function and rescue by EC transfusion are, at least in part, endothelial nitric oxide synthase mediated. Plasma asymmetric dimethylarginine was increased by Nx and decreased by EC transfusion, whereas mRNA expression of dimethylarginine dimethylaminohydrolases 1 (DDAH1) was decreased by Nx and restored by EC transfusion. Immunohistochemical staining confirmed that local expression of DDAH1 is decreased by Nx and increased by EC transfusion. In conclusion, EC transfusion attenuates Nx-induced endothelium-dependent vascular dysfunction by regulating DDAH1 expression and enhancing endothelial nitric oxide synthase activity. These results suggest that EC-based therapy could provide a novel therapeutic strategy to improve vascular function in chronic kidney disease.

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Role of miR-124 and miR-141 in the regulation of vascular reactivity and the relationship to RhoA and Rac1 after hemorrhage and hypoxia

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00651.2014 ◽

2016 ◽

Vol 310 (2) ◽

pp. H206-H216 ◽

Cited By ~ 11

Author(s):

Liangming Liu ◽

Jiatao Zang ◽

Xiangyun Chen ◽

Guangming Yang ◽

Yu Zhu ◽

...

Keyword(s):

Vascular Function ◽

Vascular Reactivity ◽

Treatment Protocol ◽

Mesenteric Arteries ◽

Related Factor ◽

Mutual Regulation ◽

Vascular Hyporeactivity ◽

Regulatory Effects ◽

Underlying Mechanisms ◽

The Relationship

Recent studies show that hypoxia can alter expression levels of microRNAs (miRNAs). Whether hypoxia or hemorrhage-induced vascular hyporeactivity is related to miRNAs and the underlying mechanisms of this process is not clear. Using hypoxia-treated superior mesenteric arteries (SMAs) and vascular smooth muscle cells (VSMCs) of rats that underwent hemorrhage, we observed the regulatory effects of miR-124/miR-141 on vascular reactivity, the relationship of these miRNAs to RhoA and Rac1, and the mutual regulation of miR-124 and miR-141. The contractile responses of SMAs and VSMCs showed an increase in early stages and a decrease in late stages of hypoxia and hemorrhage. Forty-five miRNAs appeared to have been significantly changed in SMAs after hypoxia, and miR-124 and miR-141 underwent the most change. Overexpressed miR-124 or miR-141 and their antisenses appeared to alter both vascular reactivity and expression of the proteins RhoA and Rac1 after hypoxia. miR-124 inhibited Rac1 by acting at the Rac1 mRNA 3′-untranslated region (UTR), but it led to an increase in RhoA by inhibiting miR-141. miR-141 inhibited RhoA by acting at the RhoA mRNA 3′-UTR, but it led to an increase in Rac1 by inhibiting miR-124. Further study found that miR-124 inhibited miR-141 via transcription factor early growth response gene-1 (Egr-1), whereas miR-141 inhibited miR-124 via transcription of nuclear factor erythroid 2-related factor 2 (Nrf-2). These results suggest that miR-124 and miR-141 participate in the regulation of vascular reactivity after hypoxia and hemorrhage by regulating expression of the RhoA and Rac1 proteins, and in doing so, miR-124 and miR-141 are mutually regulated. These findings provide potential targets for restoring vascular function as part of the treatment protocol for hemorrhagic shock and some other critical illness.

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Far-Infrared-Emitting Sericite Board Upregulates Endothelial Nitric Oxide Synthase Activity through Increasing Biosynthesis of Tetrahydrobiopterin in Endothelial Cells

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2019/1813282 ◽

2019 ◽

Vol 2019 ◽

pp. 1-9

Author(s):

Seonhee Kim ◽

Ikjun Lee ◽

Hee-Jung Song ◽

Su-jeong Choi ◽

Harsha Nagar ◽

...

Keyword(s):

Nitric Oxide ◽

Endothelial Cells ◽

Vascular Function ◽

Vascular Endothelial Cells ◽

Umbilical Vein ◽

Vascular Diseases ◽

Far Infrared ◽

No Production ◽

Sprague Dawley ◽

Endothelial Nitric Oxide

Far-infrared ray (FIR) therapy has been reported to exert beneficial effects on cardiovascular function by elevating endothelial nitric oxide synthesis (eNOS) activity and nitric oxide (NO) production. Tetrahydrobiopterin (BH4) is a key determinant of eNOS-dependent NO synthesis in vascular endothelial cells. However, whether BH4 synthesis is associated with the effects of FIR on eNOS/NO production has not yet been investigated. In this study, we investigated the effects of FIR on BH4-dependent eNOS/NO production and vascular function. We used FIR-emitting sericite boards as an experimental material and placed human umbilical vein endothelial cells (HUVECs) and Sprague–Dawley rats on the boards with or without FIR irradiation and then evaluated vascular relaxation by detecting NO generation, BH4 synthesis, and Akt/eNOS activation. Our results showed that FIR radiation significantly enhanced Akt/eNOS phosphorylation and NO production in human endothelial cells and aorta tissues. FIR can also induce BH4 storage by elevating levels of enzymes (e.g., guanosine triphosphate cyclohydrolase-1, 6-pyruvoyl tetrahydrobiopterin synthase, sepiapterin reductase, and dihydrofolate reductase), which ultimately results in NO production. These results indicate that FIR upregulated eNOS-dependent NO generation via BH4 synthesis and Akt phosphorylation, which contributes to the regulation of vascular function. This might develop potential clinical application of FIR to treat vascular diseases by augmenting the BH4/NO pathway.

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Fetal origins of adult vascular dysfunction in mice lacking endothelial nitric oxide synthase

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00367.2004 ◽

2005 ◽

Vol 288 (5) ◽

pp. R1114-R1121 ◽

Cited By ~ 30

Author(s):

Monica Longo ◽

Venu Jain ◽

Yuri P. Vedernikov ◽

Radek Bukowski ◽

Robert E. Garfield ◽

...

Keyword(s):

Nitric Oxide ◽

Nitric Oxide Synthase ◽

Endothelial Nitric Oxide Synthase ◽

Vascular Function ◽

Vascular Dysfunction ◽

Mesenteric Arteries ◽

Fetal Origins ◽

Uterine Environment ◽

Oxide Synthase ◽

Endothelial Nitric Oxide

Epidemiological studies have shown increased incidence of hypertension and coronary artery disease in growth-restricted fetuses during their adult life. A novel animal model was used to test the hypothesis regarding the role of an abnormal uterine environment in fetal programming of adult vascular dysfunction. Mice lacking a functional endothelial nitric oxide synthase (NOS3−/−KO, where KO is knockout) and wild-type (WT) mice (NOS3+/+WT) were crossbred to produce homozygous NOS3−/−KO, maternally derived heterozygous (NOS3+/−mat, mother with NOS3 deficiency), paternally derived heterozygous (NOS3+/−pat, normal mother), and NOS3+/+WT litters. Number of fetuses per litter was smaller in NOS3−/−KO and NOS3+/−mat compared with NOS3+/−pat and NOS3+/+WT mice. Adult female mice from these litters (7–8 wk old) were killed, and ring preparations of carotid and mesenteric arteries were mounted in a wire myograph to evaluate the passive and reactive vascular characteristics. Slope of the length-tension plot (a measure of vascular compliance) was increased, and optimal diameter (as calculated by Laplace equation) was decreased in NOS3−/−KO and NOS3+/−mat compared with NOS3+/−pat and NOS3+/+WT mice. Acetylcholine caused vasorelaxation in NOS3+/−pat and NOS3+/+WT and contraction in NOS3−/−KO and NOS3+/−mat mice. Responses to phenylephrine and Ca2+ were increased in NOS3−/−KO and NOS3+/−mat compared with NOS3+/−pat and NOS3+/+WT mice. Relaxation to isoproterenol was decreased in NOS3−/−KO and NOS3+/−mat vs. NOS3+/−pat and NOS3+/+WT mice. Abnormalities in the passive and reactive in vitro vascular properties seen in NOS+/−mat that developed in a NOS3-deficient maternal/uterine environment compared with the genetically identical NOS3+/−pat mice that developed in a normal environment are the first direct evidence in support of a role for uterine environment in determining vascular function in later life.

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Improved pulmonary vascular reactivity and decreased hypertrophic remodeling during nonhypercapnic acidosis in experimental pulmonary hypertension

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00293.2011 ◽

2012 ◽

Vol 302 (9) ◽

pp. L875-L890 ◽

Cited By ~ 12

Author(s):

Helen Christou ◽

Ossama M. Reslan ◽

Virak Mam ◽

Alain F. Tanbe ◽

Sally H. Vitali ◽

...

Keyword(s):

Pulmonary Hypertension ◽

Vascular Function ◽

Vascular Reactivity ◽

Ex Vivo ◽

Systolic Pressure ◽

Mesenteric Arteries ◽

Hypoxic Exposure ◽

Sprague Dawley ◽

Vsmc Proliferation

Pulmonary hypertension (PH) is characterized by pulmonary arteriolar remodeling with excessive pulmonary vascular smooth muscle cell (VSMC) proliferation. This results in decreased responsiveness of pulmonary circulation to vasodilator therapies. We have shown that extracellular acidosis inhibits VSMC proliferation and migration in vitro. Here we tested whether induction of nonhypercapnic acidosis in vivo ameliorates PH and the underlying pulmonary vascular remodeling and dysfunction. Adult male Sprague-Dawley rats were exposed to hypoxia (8.5% O2) for 2 wk, or injected subcutaneously with monocrotaline (MCT, 60 mg/kg) to develop PH. Acidosis was induced with NH4Cl (1.5%) in the drinking water 5 days prior to and during the 2 wk of hypoxic exposure (prevention protocol), or after MCT injection from day 21 to 28 (reversal protocol). Right ventricular systolic pressure (RVSP) and Fulton's index were measured, and pulmonary arteriolar remodeling was analyzed. Pulmonary and mesenteric artery contraction to phenylephrine (Phe) and high KCl, and relaxation to acetylcholine (ACh) and sodium nitroprusside (SNP) were examined ex vivo. Hypoxic and MCT-treated rats demonstrated increased RVSP, Fulton's index, and pulmonary arteriolar thickening. In pulmonary arteries of hypoxic and MCT rats there was reduced contraction to Phe and KCl and reduced vasodilation to ACh and SNP. Acidosis prevented hypoxia-induced PH, reversed MCT-induced PH, and resulted in reduction in all indexes of PH including RVSP, Fulton's index, and pulmonary arteriolar remodeling. Pulmonary artery contraction to Phe and KCl was preserved or improved, and relaxation to ACh and SNP was enhanced in NH4Cl-treated PH animals. Acidosis alone did not affect the hemodynamics or pulmonary vascular function. Phe and KCl contraction and ACh and SNP relaxation were not different in mesenteric arteries of all groups. Thus nonhypercapnic acidosis ameliorates experimental PH, attenuates pulmonary arteriolar thickening, and enhances pulmonary vascular responsiveness to vasoconstrictor and vasodilator stimuli. Together with our finding that acidosis decreases VSMC proliferation, the results are consistent with the possibility that nonhypercapnic acidosis promotes differentiation of pulmonary VSMCs to a more contractile phenotype, which may enhance the effectiveness of vasodilator therapies in PH.

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Increased superoxide leads to decreased flow-induced dilation in resistance arteries of Mn-SOD-deficient mice

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.01036.2004 ◽

2005 ◽

Vol 288 (5) ◽

pp. H2225-H2231 ◽

Cited By ~ 12

Author(s):

Changdong Yan ◽

An Huang ◽

Zhiping Wu ◽

Pawel M. Kaminski ◽

Michael S. Wolin ◽

...

Keyword(s):

Nitric Oxide ◽

Nitric Oxide Synthase ◽

Vascular Function ◽

Manganese Superoxide Dismutase ◽

Mesenteric Arteries ◽

Resistance Arteries ◽

Enos Activity ◽

Oxide Synthase ◽

Endothelial Nitric Oxide ◽

Enos Protein

The role of mitochondrial manganese-superoxide dismutase (Mn-SOD) in the maintenance of vascular function has not yet been studied. Thus we examined flow- and agonist-induced dilations in isolated mesenteric arteries (∼90 μm in diameter) of Mn-SOD heterozygous (Mn-SOD+/−) and wild-type (WT) mice. Increases in flow elicited dilations in all vessels, but the magnitude of the dilation was significantly less in vessels of Mn-SOD+/− mice than in those of WT mice (64 vs. 74% of passive diameter). Nω-nitro-l-arginine methyl ester inhibited the dilation in vessels of WT mice but had no effect on vessels of Mn-SOD+/− mice. Tempol or tiron (superoxide scavengers) increased flow-induced dilation in vessels of Mn-SOD+/− mice. Acetylcholine- and sodium nitroprusside-induced, but not adenosine-induced, dilations were also decreased in arteries of Mn-SOD+/− mice. Superoxide levels in the arteries of Mn-SOD+/− mice were significantly increased. Western blot analysis confirmed a 50% reduction of Mn-SOD protein in the vessels of Mn-SOD+/− mice. A 41% reduction in endothelial nitric oxide synthase (eNOS) protein and a 37% reduction in eNOS activity were also found in the vessels of Mn-SOD+/− mice. Whereas there was no difference in eNOS protein in kidney homogenates of WT and Mn-SOD+/− mice, a significant reduction of nitric oxide synthase activity was found in Mn-SOD+/− mice, which could be restored by the administration of tiron. We conclude that an increased concentration of superoxide due to reduced activity of Mn-SOD, which inactivates nitric oxide and inhibits eNOS activity, contributes to the impaired vasodilator function of isolated mesenteric arteries of Mn-SOD+/− mice. These results suggest that Mn-SOD contributes significantly to the regulation of vascular function.

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The Effect on Health of Some Cardiovascular Risk Factors

Revista de Chimie ◽

10.37358/rc.17.10.5863 ◽

2017 ◽

Vol 68 (10) ◽

pp. 2237-2242

Author(s):

Germaine Savoiu Balint ◽

Mihaiela Andoni ◽

Ramona Amina Popovici ◽

Laura Cristina Rusu ◽

Ioana Citu ◽

...

Keyword(s):

Nitric Oxide ◽

Vascular Reactivity ◽

Vascular Wall ◽

Dose Effect ◽

Organ Bath ◽

Before And After ◽

Specific Receptors ◽

Oxide Synthase ◽

Endothelial Nitric Oxide ◽

Relaxing Response

Arterial endothelium produces a large ramge of active factors which are indispensable for modulation of vasomotor tone and maintenance of vascular wall integrity. From these factors, nitric oxide (NO), wich is released by the endothelial cells as a response to acetylcholine or adenosine action on specific receptors, plays an important role.NO is the result of oxidation process of L-arginine into L-citrulline, under the action of endothelial nitric oxide synthase (NOSe), wich is activated by intracelluar Ca2+ - calmodulin complex . Our study, performed in isolated organ bath, analyzed vascular reactivity of 12 guinea pigs� thoracic aorta rings. After phenylephrine -PHE 10-5 mol/L precontraction, the dose-effect curves for acetylcoline � ACH, adenosine 5� phosphate - 5�ADP and sodium nitroprusside � SNP were determined, before and after incubation of preparation, for 1 hour, with 5% hydrosoluble cigarettes smoke extract (CSE). Statistic analysis, performed with the use of t pair test and ANOVA parametric test, showed that incubation of vascular preparation with 5% CSE has increased the contractile response to PHE 10-5 mol/L (p[0.05), has reduced the endothelium-dependent relaxing response to ATP 10-5 mol/L (p[0.001) and 5�ADP 10-5 molo/L (p[0.001), but has not significantly modified the endothelium-independent relaxing response to SNP 10-5 mol/L (p=0.05). As a conclusion, vascular rings incubation with 5% CSE induced a decrease of endothelium NO synthesis under the action of AXH and 5�ADP, but did not change the smooth muscle fiber respomse in the presence of NO released by SNP.

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