Stress In Human Hypertension Research Articles

Reactive oxygen species and vascular biology: implications in human hypertension

Increased vascular production of reactive oxygen species (ROS; termed oxidative stress) has been implicated in various chronic diseases, including hypertension. Oxidative stress is both a cause and a consequence of hypertension. Although oxidative injury may not be the sole etiology, it amplifies blood pressure elevation in the presence of other pro-hypertensive factors. Oxidative stress is a multisystem phenomenon in hypertension and involves the heart, kidneys, nervous system, vessels and possibly the immune system. Compelling experimental and clinical evidence indicates the importance of the vasculature in the pathophysiology of hypertension and as such much emphasis has been placed on the (patho)biology of ROS in the vascular system. A major source for cardiovascular, renal and neural ROS is a family of non-phagocytic nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (Nox), including the prototypic Nox2 homolog-based NADPH oxidase, as well as other Noxes, such as Nox1 and Nox4. Nox-derived ROS is important in regulating endothelial function and vascular tone. Oxidative stress is implicated in endothelial dysfunction, inflammation, hypertrophy, apoptosis, migration, fibrosis, angiogenesis and rarefaction, important processes involved in vascular remodeling in hypertension. Despite a plethora of data implicating oxidative stress as a causative factor in experimental hypertension, findings in human hypertension are less conclusive. This review highlights the importance of ROS in vascular biology and focuses on the potential role of oxidative stress in human hypertension.

Inadequate Cytoplasmic Antioxidant Enzymes Response Contributes to the Oxidative Stress in Human Hypertension

Untreated hypertensive patients show increased oxidative stress and decreased antioxidant enzyme activity in mononuclear cells. Therefore, the objective of this study was to determine whether or not the low antioxidant enzyme activity observed in mononuclear cells of hypertensive subjects is in part dependent on a defective activity of antioxidant mechanisms. Activity and mRNA level of antioxidant enzymes, CuZn- and Mn-superoxide dismutases, catalase, glutathione peroxidase type 1, and glutathione reductase were simultaneously measured in mononuclear cells of controls (n = 38) and hypertensive subjects (n = 35), in the absence of and during antihypertensive treatment. An increase in oxidative stress and a decrease in the activity of cytoplasmic enzymes were observed in untreated hypertensive patients. Concurrently, CuZn-superoxide dismutase and glutathione reductase mRNA levels were significantly reduced, and glutathione peroxidase type 1 mRNA was slightly reduced. In contrast, increased activity and mRNA levels of the mitochondrial Mn-superoxide dismutase were observed. Antihypertensive treatment, nonpharmacologic with or without a drug regimen of beta-blocker or angiotensin AT1 receptor blocker was administered for a 3-month period. Afterward, after the improvement in oxidative stress during treatment, a recovery of the cytoplasmic antioxidant enzymatic activity and a more profound decrease in mRNA levels were observed for CuZn-superoxide dismutase, glutathione peroxidase type 1, and glutathione reductase. Meanwhile mitochondrial enzymatic activity decreased, as did the mRNA level. The inadequate response of the main cytoplasmatic antioxidant systems, as well as of the enzymes participating in the maintenance of glutathione levels, may contribute to the vulnerability of hypertensives to oxidative stress.

Downregulation of cytoplasmic antioxidant enzymes contributes to the oxidative stress in human hypertension

Downregulation of cytoplasmic antioxidant enzymes contributes to the oxidative stress in human hypertension

Oxidative stress in human hypertension: association with antihypertensive treatment, gender, nutrition, and lifestyle

There is growing evidence that oxidative stress contributes to the pathogenesis of hypertension. Our aim was to measure markers of oxidative stress in hypertensive subjects, and assess the potential confounding influences of antihypertensive therapy, other cardiovascular risk factors, gender, lifestyle, and nutrition. Markers of oxidative stress, including plasma and 24 h urinary F 2-isoprostanes, were measured in 70 untreated (men = 43, women = 27) and 85 treated (men = 43, women = 42) hypertensive subjects and 40 normotensive controls (men = 20, women = 20). Overall, F 2-isoprostanes were not elevated in hypertensive subjects compared with controls. However, urinary and plasma F 2-isoprostanes were significantly lower in treated compared with untreated hypertensive men, but not women. In hypertensive men, the number of antihypertensive drugs taken was inversely associated with both urinary and plasma F 2-isoprostanes ( p < .05). Self-reported alcohol intake and biomarkers of alcohol consumption (γ-glutamyl transpeptidase and high-density lipoprotein cholesterol) were positively associated with plasma but not urinary, F 2-isoprostanes in men. Several nutrients were independently associated with plasma and urinary F 2-isoprostanes in women. The results do not support the hypothesis that treated or untreated hypertensive subjects are under increased oxidative stress compared with normotensive controls.

The influence of long-term ACE inhibitor treatment on circulatory responses to stress in human hypertension

The objective of the study was to examine the influence of angiotensin converting enzyme (ACE) inhibition on circulatory responses to standardized stress tests in primary mild to moderate hypertension. Patients (n = 28) received 5 mg ramipril daily or placebo for 6 weeks in a double-blind crossover design, followed by 6 months of open ramipril treatment. Mental stress (a 20-min Stroop’s color word conflict test) and a cold pressor test were performed at the end of each of the three study periods. Noninvasive blood pressure and heart rate were recorded. Ramipril reduced systolic and diastolic blood pressure levels at rest (from 146 ± 3/99 ± 3 with placebo to 135 ± 4/94 ± 3 at 6 weeks, and 136 ± 4/91 ± 3 mm Hg at 6 months, in the laboratory) and during mental stress. Resting heart rates were unchanged by ramipril. Ramipril reduced systolic blood pressure and heart rate responses during mental stress; diastolic blood pressure responses were unchanged. Ramipril reduced cardiac workload (systolic blood pressure × heart rate) levels and responses. Treatment effects at 6 months were generally greater than at 6 weeks. During the cold pressor test systolic and diastolic blood pressure levels were lowered by ramipril, but responses were unchanged. Heart rate responses, however, were reduced. Thus, ramipril reduced cardiac workload levels and responses also during the cold pressor test. These findings show that ACE inhibitors can reduce cardiac workload during stressful situations. If confirmed, this would seem to offer an advantage in the treatment of hypertension.