The Effect on Health of Some Cardiovascular Risk Factors

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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Adventitial Gene Transfer of Recombinant Endothelial Nitric Oxide Synthase to Rabbit Carotid Arteries Alters Vascular Reactivity

Circulation ◽

10.1161/01.cir.96.7.2254 ◽

1997 ◽

Vol 96 (7) ◽

pp. 2254-2261 ◽

Cited By ~ 56

Author(s):

Iftikhar J. Kullo ◽

Geza Mozes ◽

Robert S. Schwartz ◽

Peter Gloviczki ◽

Thomas B. Crotty ◽

...

Keyword(s):

Nitric Oxide ◽

Nitric Oxide Synthase ◽

Gene Transfer ◽

Endothelial Nitric Oxide Synthase ◽

Vascular Reactivity ◽

Carotid Arteries ◽

Oxide Synthase ◽

Endothelial Nitric Oxide

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Nitric oxide function in atherosclerosis

Mediators of Inflammation ◽

10.1080/09629359791875 ◽

1997 ◽

Vol 6 (1) ◽

pp. 3-21 ◽

Cited By ~ 29

Author(s):

K. E. Matthys ◽

H. Bult

Keyword(s):

Nitric Oxide ◽

Leukocyte Adhesion ◽

Atherosclerotic Lesion ◽

Vascular Wall ◽

Early Event ◽

No Production ◽

Oxygen Intermediates ◽

Atherosclerotic Lesions ◽

Oxide Synthase ◽

Endothelial Nitric Oxide

Atherosclerosis is a chronic inflammatory process in the intima of conduit arteries, which disturbs the endothelium-dependent regulation of the vascular tone by the labile liposoluble radical nitric oxide (NO) formed by the constitutive endothelial nitric oxide synthase (eNOS). This defect predisposes to coronary vasospasm and cardiac ischaemia, with anginal pain as the typical clinical manifestation. It is now appreciated that endothelial dysfunction is an early event in atherogenesis and that it may also involve the microcirculation, in which atherosclerotic lesions do not develop. On the other hand, the inflammatory environment in atherosclerotic plaques may result in the expression of the inducible NO synthase (iNOS) isozyme. Whether the dysfunction in endothelial NO production is causal to, or the result of, atherosclerotic lesion formation is still highly debated. Most evidence supports the hypothesis that constitutive endothelial NO release protects against atherogenesis e.g. by preventing smooth muscle cell proliferation and leukocyte adhesion. Nitric oxide generated by the inducible isozyme may be beneficial by replacing the failing endothelial production but excessive release may damage the vascular wall cells, especially in combination with reactive oxygen intermediates.

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146 Adenoviral-mediated gene transfer of endothelial nitric oxide synthase to the rabbit carotid artery alters vascular reactivity

Atherosclerosis ◽

10.1016/s0021-9150(97)87568-5 ◽

1997 ◽

Vol 130 ◽

pp. S38

Author(s):

I. Kullo ◽

G. Mozes ◽

R. Schwartz ◽

P. Gloviczki ◽

T. Crotty ◽

...

Keyword(s):

Nitric Oxide ◽

Nitric Oxide Synthase ◽

Gene Transfer ◽

Carotid Artery ◽

Endothelial Nitric Oxide Synthase ◽

Vascular Reactivity ◽

Rabbit Carotid Artery ◽

Oxide Synthase ◽

Endothelial Nitric Oxide

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Adenosine-mediated alteration of vascular reactivity and inflammation in a murine model of asthma

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.01224.2007 ◽

2008 ◽

Vol 294 (5) ◽

pp. H2158-H2165 ◽

Cited By ~ 16

Author(s):

Dovenia S. Ponnoth ◽

Ahmed Nadeem ◽

S. Jamal Mustafa

Keyword(s):

Systemic Inflammation ◽

Endothelial Nitric Oxide Synthase ◽

Cardiovascular Events ◽

Vascular Reactivity ◽

Allergen Challenge ◽

Organ Bath ◽

Vascular Responses ◽

Oxide Synthase ◽

Endothelial Nitric Oxide ◽

Allergic Mouse

Chronic respiratory disorders such as asthma are believed to be associated with adverse cardiovascular events. We hypothesize that asthmatic inflammation translates into systemic inflammation and alters vascular responses where adenosine (AD) plays an important role. Therefore, this study investigated the effects of aerosolized AD, used to elevate lung AD levels, on vascular reactivity and inflammation in our allergic mouse model of asthma. Balb/c mice were divided into four groups: control (Con), Con + aerosolized AD (Con + AD), allergen sensitized and challenged (Sen), and Sen + aerosolized AD (Sen + AD). The animals were sensitized with ragweed (200 μg ip) on days 1 and 6, followed by 1% ragweed aerosol challenges from days 11 to 13. On day 14, the Con + AD and Sen + AD groups received a single AD aerosol challenge (6 mg/ml) for 2 min, followed by the collection of the aorta and plasma on day 15. Organ bath experiments showed concentration-dependent aortic relaxations to AD in the Con and Con + AD groups, which were impaired in the Sen and Sen + AD groups. Real-time PCR data showed changes in aortic AD receptors (ARs), with the expression of A1ARs upregulated, whereas the expression of A2ARs and endothelial nitric oxide synthase genes were downregulated, resulting in an impairment of vasorelaxation in the Sen and Sen + AD groups. The A1AR antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) reversed the impairment in vasorelaxation observed in the Sen and Sen + AD groups, whereas the A2BAR antagonist alloxazine inhibited vasorelaxation in all groups. Allergen challenge caused systemic inflammation in allergic mice, with AD aerosol further enhancing it as determined by the inflammatory cytokines profile in plasma. In conclusion, asthmatic mice showed altered vascular reactivity and systemic inflammation, with AD aerosol further exacerbating these effects.

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Heat shock protein 90 modulates endothelial nitric oxide synthase activity and vascular reactivity in the newborn piglet pulmonary circulation

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00252.2006 ◽

2007 ◽

Vol 292 (6) ◽

pp. L1515-L1525 ◽

Cited By ~ 24

Author(s):

Judy L. Aschner ◽

Susan L. Foster ◽

Mark Kaplowitz ◽

Yongmei Zhang ◽

Heng Zeng ◽

...

Keyword(s):

Nitric Oxide ◽

Heat Shock ◽

Nitric Oxide Synthase ◽

Heat Shock Protein ◽

Pulmonary Circulation ◽

Endothelial Nitric Oxide Synthase ◽

Vascular Reactivity ◽

Heat Shock Protein 90 ◽

Oxide Synthase ◽

Endothelial Nitric Oxide

Heat shock protein 90 (Hsp90) binding to endothelial nitric oxide synthase (eNOS) is an important step in eNOS activation. The conformational state of bound Hsp90 determines whether eNOS produces nitric oxide (NO) or superoxide (O2•−). We determined the effects of the Hsp90 antagonists geldanamycin (GA) and radicicol (RA) on basal and ACh-stimulated changes in vessel diameter, cGMP production, and Hsp90:eNOS coimmunoprecipitation in piglet resistance level pulmonary arteries (PRA). In perfused piglet lungs, we evaluated the effects of GA and RA on ACh-stimulated changes in pulmonary arterial pressure (Ppa) and perfusate accumulation of stable NO metabolites (NOx−). The effects of GA and RA on ACh-stimulated O2•− generation was investigated in cultured pulmonary microvascular endothelial cells (PMVEC) by dihydroethidine (DHE) oxidation and confocal microscopy. Hsp90 inhibition with GA or RA reduced ACh-mediated dilation, abolished the ACh-stimulated increase in cGMP, and reduced eNOS:Hsp90 coprecipitation. GA and RA also inhibited the ACh-mediated changes in Ppa and NOx− accumulation rates in perfused lungs. ACh increased the rate of DHE oxidation in PMVEC pretreated with GA and RA but not in untreated cells. The cell-permeable superoxide dismutase mimetic M40401 reversed GA-mediated inhibition of ACh-induced dilation in PRA. We conclude that Hsp90 is a modulator of eNOS activity and vascular reactivity in the newborn piglet pulmonary circulation. Uncoupling of eNOS with GA or RA inhibits ACh-mediated dilation by a mechanism that involves O2•− generation.

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