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Pharmaceuticals (Basel, Switzerland) Aug 2023Normal tension glaucoma (NTG) is defined as a subtype of primary open-angle glaucoma (POAG) in which the intraocular pressure (IOP) values are constantly within the... (Review)
Review
Normal tension glaucoma (NTG) is defined as a subtype of primary open-angle glaucoma (POAG) in which the intraocular pressure (IOP) values are constantly within the statistically normal range without treatment and represents approximately the 30-40% of all glaucomatous cases. The pathophysiology of this condition is multifactorial and is still not completely well known. Several theories have been proposed to explain the onset and progression of this disease, which can be divided into IOP-dependent and IOP-independent factors, suggesting different therapeutic strategies. The current literature strongly supports the fundamental role of IOP in NTG. The gold standard treatment for NTG tends to be based on the lowering IOP even if "statistically normal". Numerous studies have shown, however, that the IOP reduction alone is not enough to slow down or stop the disease progression in all cases, suggesting that other IOP-independent risk factors may contribute to the NTG pathogenesis. In addition to IOP-lowering strategies, several different therapeutic approaches for NTG have been proposed, based on vaso-active, antioxidant, anti-inflammatory and/or neuroprotective substances. To date, unfortunately, there are no standardized or proven treatment alternatives for NTG when compared to traditional IOP reduction treatment regimes. The efficacy of the IOP-independent strategies in decreasing the risk or treating NTG still remains inconclusive. The aim of this review is to highlight strategies reported in the current literature to treat NTG. The paper also describes the challenges in finding appropriate and pertinent treatments for this potentially vision-threatening disease. Further comprehension of NTG pathophysiology can help clinicians determine when to use IOP-lowering treatments alone and when to consider additional or alternatively individualized therapies focused on particular risk factors, on a case-by-case basis.
PubMed: 37631087
DOI: 10.3390/ph16081172 -
International Journal of Molecular... Dec 2023The pathogenesis of complex diseases such as pulmonary arterial hypertension (PAH) is entirely rooted in changes in the expression of some vasoactive factors. These play... (Review)
Review
The pathogenesis of complex diseases such as pulmonary arterial hypertension (PAH) is entirely rooted in changes in the expression of some vasoactive factors. These play a significant role in the onset and progression of the disease. Indeed, PAH has been associated with pathophysiologic alterations in vascular function. These are often dictated by increased oxidative stress and impaired modulation of the nitric oxide (NO) pathway. NO reduces the uncontrolled proliferation of vascular smooth muscle cells that leads to occlusion of vessels and an increase in pulmonary vascular resistances, which is the mainstay of PAH development. To date, two classes of NO-pathway modulating drugs are approved for the treatment of PAH: the phosphodiesterase-5 inhibitors (PD5i), sildenafil and tadalafil, and the soluble guanylate cyclase activator (sGC), riociguat. Both drugs provide considerable improvement in exercise capacity and pulmonary hemodynamics. PD5i are the recommended drugs for first-line PAH treatment, whereas sGCs are also the only drug approved for the treatment of resistant or inoperable chronic thromboembolic pulmonary hypertension. In this review, we will focus on the current information regarding the nitric oxide pathway and its modulation in PAH.
Topics: Humans; Pulmonary Arterial Hypertension; Nitric Oxide; Familial Primary Pulmonary Hypertension; Phosphodiesterase 5 Inhibitors; Sildenafil Citrate; Soluble Guanylyl Cyclase
PubMed: 38203205
DOI: 10.3390/ijms25010036 -
International Journal of Molecular... May 2024Sepsis-associated kidney injury is common in critically ill patients and significantly increases morbidity and mortality rates. Several complex pathophysiological... (Review)
Review
Sepsis-associated kidney injury is common in critically ill patients and significantly increases morbidity and mortality rates. Several complex pathophysiological factors contribute to its presentation and perpetuation, including macrocirculatory and microcirculatory changes, mitochondrial dysfunction, and metabolic reprogramming. Recovery from acute kidney injury (AKI) relies on the evolution towards adaptive mechanisms such as endothelial repair and tubular cell regeneration, while maladaptive repair increases the risk of progression to chronic kidney disease. Fundamental management strategies include early sepsis recognition and prompt treatment, through the administration of adequate antimicrobial agents, fluid resuscitation, and vasoactive agents as needed. In septic patients, organ-specific support is often required, particularly renal replacement therapy (RRT) in the setting of severe AKI, although ongoing debates persist regarding the ideal timing of initiation and dosing of RRT. A comprehensive approach integrating early recognition, targeted interventions, and close monitoring is essential to mitigate the burden of SA-AKI and improve patient outcomes in critical care settings.
Topics: Humans; Acute Kidney Injury; Sepsis; Renal Replacement Therapy; Critical Illness
PubMed: 38892111
DOI: 10.3390/ijms25115924 -
American Journal of Physiology.... Oct 2023Obesity is associated with hypertension. However, the mechanisms involved are not fully understood. Therefore, we investigated the relationship between obesity and...
Obesity is associated with hypertension. However, the mechanisms involved are not fully understood. Therefore, we investigated the relationship between obesity and vasoactive mediators. In this cross-sectional study, blood pressure (BP) and vasoactive mediators of hypertension are compared among 135 adults in the nonobese, obese, and morbidly obese body mass index (BMI) ranges (BMI ≤27, 30-40, and >40 kg/m, respectively). Angiotensinogen, angiotensin II, renin, aldosterone, endothelin-1 (ET-1), neprilysin, atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), cyclic guanosine monophosphate (cGMP), and cyclic adenosine monophosphate (cAMP) levels were measured and their relationship to BP, BMI, race, and gender were investigated. Systolic and diastolic BP (SBP and DSP) were significantly higher in subjects with obesity and morbid obesity compared with nonobese. Angiotensin II, ET-1, and neprilysin were significantly higher in subjects with morbid obesity while BNP was lower. Levels of angiotensinogen, renin, aldosterone, ANP, cGMP, and cAMP did not differ between the groups. BMI was positively related to SBP, DBP, angiotensin II, ET-1, and neprilysin, and inversely related to cGMP and BNP. Age, male gender, and African-American race were associated with higher SBP. SBP was positively related to angiotensin II and ET-1 and inversely related to aldosterone, renin, and cGMP. On multivariate analyses, age, BMI, gender, and race were the main determinants of SBP, and excluding these variables, angiotensin II, aldosterone, renin, and ET-1 accounted for 21.1% ability to predict SBP. Obesity, especially morbid obesity, is associated with higher BP, higher angiotensin II and ET-1 (vasoconstrictors), and lower levels BNP and cGMP (vasodilators). SBP variability can be partly explained by angiotensin II, aldosterone, renin, and ET-1. Our data show that obesity, especially morbid obesity, is associated with higher blood pressure levels and increases angiotensin II and endotherlin-1 (ET-1) (vasoconstrictors) and lower levels BNP and cGMP (vasodilators) and that systolic blood pressure variability can be partly explained by levels of angiotensin II, aldosterone, renin, and ET-1. The effect of these mediators on blood pressure is in addition to the effects of other known factors related to age, male gender, and AA race.
Topics: Adult; Humans; Male; Renin; Angiotensinogen; Renin-Angiotensin System; Obesity, Morbid; Aldosterone; Angiotensin II; Cross-Sectional Studies; Neprilysin; Hypertension; Blood Pressure; Vasodilator Agents; Vasoconstrictor Agents
PubMed: 37672250
DOI: 10.1152/ajpendo.00209.2022 -
Cureus Dec 2023Tea and coffee have become ingrained in our daily lives and have become the most widely consumed drinks after water. Their effects vary on an individual basis depending... (Review)
Review
Tea and coffee have become ingrained in our daily lives and have become the most widely consumed drinks after water. Their effects vary on an individual basis depending upon the amount of daily consumption, genetic polymorphisms, and the presence of comorbidities. Non-habitual individuals experience an initial, brief increase in blood pressure due to caffeine's vasoactive effects. Caffeine also appears to be protective against arrhythmias and heart failure. Along with having a generally cardioprotective profile, they have also demonstrated to have a favorable impact on insulin resistance and reduced risk of diabetes mellitus. Physicians often practice caution and advise patients with known cardiovascular diseases to refrain from drinking caffeine; however, studies have shown that drinking two to three cups a day has either no or some beneficial effects on both patients with or without cardiac disorders like arrhythmias. This article focuses on the effects of tea and coffee on the cardiovascular system as well as the potential mechanisms involved.
PubMed: 38186410
DOI: 10.7759/cureus.49991 -
European Journal of Pharmacology Nov 2023Vascular tone regulation is a key event in controlling blood flow in the body. Endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) help regulate the... (Review)
Review
Vascular tone regulation is a key event in controlling blood flow in the body. Endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) help regulate the vascular tone. Abnormal vascular responsiveness to various stimuli, including constrictors and dilators, has been observed in pathophysiological states although EC and VSMC coordinate to maintain the exquisite balance between contraction and relaxation in vasculatures. Thus, investigating the mechanisms underlying vascular tone abnormality is very important in maintaining vascular health and treating vasculopathy. Increased intracellular free Ca concentration ([Ca]i) is one of the major triggers initiating each EC and VSMC response. Transient receptor potential vanilloid family member 4 (TRPV4) is a Ca-permeable non-selective ion channel, which is activated by several stimuli, and is presented in both ECs and VSMCs. Therefore, TRPV4 plays an important role in vascular responses. Emerging evidence indicates the role of TRPV4 on the functions of ECs and VSMCs in various pathophysiological states, including hypertension, diabetes, and obesity. This review focused on the link between TRPV4 and the functions of ECs/VSMCs, particularly its role in vascular tone and responsiveness to vasoactive substances.
Topics: Humans; TRPV Cation Channels; Endothelial Cells; Hypertension; Hemodynamics; Endothelium, Vascular
PubMed: 37802278
DOI: 10.1016/j.ejphar.2023.176104