Advances in Pharmacologic Modulation of Nitric Oxide in Hypertension

Mizuno, Yoshiko; Jacob, Robert F.; Mason, R. Preston

doi:10.1007/s11886-010-0142-5

Cited by 15 publications

(12 citation statements)

References 69 publications

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“…However, individuals living in the Gulf region most likely experienced repeated exposures to COREXIT. Repeated exposures may potentially result in prolonged changes in cardiovascular function and ultimately contribute to the development of hypertension and other cardiovascular diseases (Bartolomucci et al 2009;Granger et al 2010;Mizuno et al 2010). Additional research examining the effects of repeated exposures to COREXIT needs to be undertaken to determine potential adverse health risks of this dispersant.…”

Section: Discussionmentioning

confidence: 99%

Acute Effects of COREXIT EC9500A on Cardiovascular Functions in Rats

Krajnak

Kan

Waugh

et al. 2011

Journal of Toxicology and Environmental Health, Part A

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These studies characterized cardiovascular responses after an acute inhalation exposure to COREXIT EC9500A, the oil dispersant used in the Deepwater Horizon oil spill. Male Sprague-Dawley rats underwent a single 5-h inhalation exposure to COREXIT EC9500A (average exposure level 27.12 mg/m(3)) or air. On d 1 and 7 following the exposure, rats were implanted with indwelling catheters and changes in heart rate and blood pressure were assessed in response to increasing levels of adrenoreceptor agonists. A separate group of rats was euthanized at the same time points, ventral tail arteries were dissected, and vascular tone along with dose-dependent responses to vasoconstricting and dilating factors were assessed in vitro. Agonist-induced dose-dependent increases in heart rate and blood pressure were greater in COREXIT EC9500A-exposed than in air-exposed rats at 1 d but not 7 d after the exposure. COREXIT EC9500A exposure also induced a rise in basal tone and reduced responsiveness of tail arteries to acetylcholine-induced vasodilation at 1 d but not 7 d following the exposure. These findings demonstrate that an acute exposure to COREXIT EC9500A exerts transient effects on cardiovascular and peripheral vascular functions.

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Section: Discussionmentioning

confidence: 99%

Acute Effects of COREXIT EC9500A on Cardiovascular Functions in Rats

Krajnak

Kan

Waugh

et al. 2011

Journal of Toxicology and Environmental Health, Part A

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“…Binding of NO, to the reduced heme moiety of sGC increases the conversion of guanosine triphosphate (GTP) to cGMP, which in turn activates downstream effector systems such as protein kinases, phosphodiesterases, and ion channels (Murad, 1986). Dysfunction of this pathway has been reported to contribute to the pathogenesis of many disorders, including hypertension and atherosclerosis (Ruetten et al, 1999; Mizuno et al, 2010). Genetic deletion of sGC results in reduced endothelial-dependent relaxation, reduced ability of NO to relax smooth muscle and prevent platelet activation and hypertension (Buys et al, 2008; Dangel et al, 2010; Groneberg et al, 2010).…”

Section: Functional Mechamisms Of Nomentioning

confidence: 99%

Post-translational regulation of endothelial nitric oxide synthase in vascular endothelium

2013

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Nitric oxide (NO) is a short-lived gaseous signaling molecule. In blood vessels, it is synthesized in a dynamic fashion by endothelial nitric oxide synthase (eNOS) and influences vascular function via two distinct mechanisms, the activation of soluble guanylyl cyclase (sGC)/cyclic guanosine monophosphate (cGMP)-dependent signaling and the S-nitrosylation of proteins with reactive thiols (S-nitrosylation). The regulation of eNOS activity and NO bioavailability is critical to maintain blood vessel function. The activity of eNOS and ability to generate NO is regulated at the transcriptional, posttranscriptional, and posttranslational levels. Post-translational modifications acutely impact eNOS activity and dysregulation of these mechanisms compromise eNOS activity and foster the development of cardiovascular diseases (CVDs). This review will intergrate past and current literature on the post-translational modifications of eNOS in both health and disease.

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“…Endothelial dysfunction itself has been shown to be directly associated with hypertension, and is thought to contribute to functional abnormalities in resistance vessels (eg, impaired endothelial-dependent vasodilation) observed in patients with hypertension 35,36. Not only is free radical-related reduction in NO bioavailability a major cause of endothelial dysfunction in patients with hypertension, but it is thought that oxidative stress could be a common mechanism of endothelial dysfunction associated with other CV risk factors 31…”

Section: Role Of Nitric Oxide In Atherosclerosismentioning

confidence: 99%

Optimal therapeutic strategy for treating patients with hypertension and atherosclerosis: focus on olmesartan medoxomil

Mason¹

2011

VHRM

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Cardiovascular (CV) disease is a major factor in mortality rates around the world and contributes to more than one-third of deaths in the US. The underlying cause of CV disease is atherosclerosis, a chronic inflammatory process that is clinically manifested as coronary artery disease, carotid artery disease, or peripheral artery disease. It has been predicted that atherosclerosis will be the primary cause of death in the world by 2020. Consequently, developing a treatment regimen that can slow or even reverse the atherosclerotic process is imperative. Atherogenesis is initiated by endothelial injury due to oxidative stress associated with CV risk factors including diabetes mellitus, hypertension, cigarette smoking, dyslipidemia, obesity, and metabolic syndrome. Since the renin–angiotensin–aldosterone system (RAAS) plays a key role in vascular inflammatory responses, hypertension treatment with RAAS-blocking agents (angiotensin-converting enzyme inhibitors [ACEIs] and angiotensin II receptor blockers [ARBs]) may slow inflammatory processes and disease progression. Reduced nitric oxide (NO) bioavailability has an important role in the process of endothelial dysfunction and hypertension. Therefore, agents that increase NO and decrease oxidative stress, such as ARBs and ACEIs, may interfere with atherosclerosis. Studies show that angiotensin II type 1 receptor antagonism with an ARB improves endothelial function and reduces atherogenesis. In patients with hypertension, the ARB olmesartan medoxomil provides effective blood pressure lowering, with inflammatory marker studies demonstrating significant RAAS suppression. Several prospective, randomized studies show vascular benefits with olmesartan medoxomil: reduced progression of coronary atherosclerosis in patients with stable angina pectoris (OLIVUS); decreased vascular inflammatory markers in patients with hypertension and micro- (pre-clinical) inflammation (EUTOPIA); improved common carotid intima-media thickness and plaque volume in patients with diagnosed atherosclerosis (MORE); and resistance vessel remodeling in patients with stage 1 hypertension (VIOS). Although CV outcomes were not assessed in these studies, the observed benefits in surrogate endpoints of disease suggest that RAAS suppression with olmesartan medoxomil may potentially have beneficial effects on CV outcomes in these patient populations.

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Advances in Pharmacologic Modulation of Nitric Oxide in Hypertension

Cited by 15 publications

References 69 publications

Acute Effects of COREXIT EC9500A on Cardiovascular Functions in Rats

Acute Effects of COREXIT EC9500A on Cardiovascular Functions in Rats

Post-translational regulation of endothelial nitric oxide synthase in vascular endothelium

Optimal therapeutic strategy for treating patients with hypertension and atherosclerosis: focus on olmesartan medoxomil

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