Is Central Nitric Oxide Essential in Hypertension?

Journal of Hypertension. Sep, 2005  |  Pubmed ID: 16093906

Different Effects of Angiotensin Receptor Blockade on End-organ Damage in Salt-dependent and Salt-independent Hypertension

Circulation. Aug, 2006  |  Pubmed ID: 16923758

Although angiotensin II type 1 receptor blockers have emerged as effective antihypertensive agents, it is not known how efficacious these agents are in treating hypertension-associated target organ damage.

Action of Thiazide on Renal Interstitial Calcium

American Journal of Hypertension. Jul, 2008  |  Pubmed ID: 18451809

Although thiazides increase urinary sodium excretion, they also decrease urinary calcium excretion. Recent studies in our laboratory have shown that increased dietary salt significantly reduces interstitial fluid calcium in Dahl salt-sensitive (DS) rats, and this was associated with a rise in blood pressure and increased urinary calcium excretion. Owing to the vasorelaxant actions of increased extracellular fluid calcium, we reasoned that the antihypertensive action of hydrochlorothiazide (HCTZ), a commonly used thiazide, may be the result of increased interstitial fluid calcium as a consequence of decreased urinary calcium excretion.

Psychosocial Factors Contribute to Resting Blood Pressure in African Americans

Ethnicity & Disease. 2008  |  Pubmed ID: 18785441

African Americans as a group have higher blood pressure than individuals of northern European ancestry (non-Hispanic Whites). We investigate whether psychosocial factors explain the resting blood pressure of healthy, community-dwelling African Americans in our study.

The Effect of Salt on Renal Damage in ENOS-deficient Mice

Hypertension Research : Official Journal of the Japanese Society of Hypertension. Feb, 2010  |  Pubmed ID: 19960018

African Americans have an increased incidence of end-stage renal disease and are characterized as having reduced bioavailability of nitric oxide and salt-sensitivity. We propose that endothelial nitric oxide synthase (eNOS) knockout mice (eNOS(-/-)) are a suitable model of hypertension-associated renal injury as seen in African Americans. Therefore, the purpose of this study was to determine whether older eNOS(-/-) mice have hypertension-associated renal injury and if dietary salt modulates this injury. Six-month-old eNOS(-/-) mice were placed on 0.12%, 0.45% or 8% NaCl diet for 8 weeks and blood pressure measured weekly; kidneys were collected for pathology evaluation and scoring at the end of the 8-week period. Mice deficient of eNOS were hypertensive at baseline compared with control mice in all three groups (128+/-3 vs. 112+/-3, P<0.05). Blood pressure was significantly elevated from baseline in eNOS(-/-) on 0.45 and 8% salt diets (P<0.02). The composite renal pathology scores for eNOS(-/-) mice were significantly greater than wild-type mice, indicating high salt intake exacerbates the injury (P<0.001 vs. normal salt diet). eNOS(-/-) mice may be used as a model of salt-induced and hypertension-associated renal injury as seen in African Americans.

Physiological Stress Increases Renal Injury in ENOS-knockout Mice

Hypertension Research : Official Journal of the Japanese Society of Hypertension. Dec, 2011  |  Pubmed ID: 22170389

African Americans have a fourfold greater likelihood of developing end-stage renal disease (ESRD) compared with Caucasians. It has been proposed that the increased prevalence may be explained by non-traditional factors such as environmental stress and psychosocial factors. In this study, we used infrequent running to exhaustion as a physiological stressor to mimic real life experiences, such walking up stairs when an elevator is malfunctioning or running to catch a bus, to study its effect on renal injury in a hypertensive mouse model (endothelial nitric oxide synthase-deficient mice; eNOS(-/-)). This model has previously been shown to have renal injury comparable to that observed in African Americans. The effect of physiological stress on renal injury was examined in the setting of low (0.12%), control (0.45%) and high (8%) dietary salt. Following bouts of physiological stress, eNOS(-/-) mice had significantly greater interstitial inflammation compared with unstressed eNOS(-/-) mice (two-way analysis of variance (2-ANOVA), Holm-Sidak; P<0.01). Interestingly, eNOS(-/-) mice on a high-salt diet had greater interstitial inflammation compared with similarly stressed eNOS(-/-) mice on a low- or control-salt diet (2-ANOVA, Holm-Sidak; P<0.03). These effects of stress were independent of systolic blood pressure (141±7, 143±4, and 158±8 vs. 141±4, 138±5, 150±4 mm Hg; end of study vs. baseline, respectively). There was no significant effect of stress or dietary salt on renal injury in control wild-type mice (eNOS(+)/(+)). These data demonstrate that physiological stress exacerbates the renal injury associated with hypertension and that high-salt compounds this effect of stress. These results provide support for the idea that psychosocial and environmental factors contribute to the increased prevalence of ESRD in hypertensive African Americans.Hypertension Research advance online publication, 15 December 2011; doi:10.1038/hr.2011.185.

State Anxiety is Associated with Cardiovascular Reactivity in Young, Healthy African Americans

International Journal of Hypertension. 2012  |  Pubmed ID: 22263105

Although several studies have shown that enhanced cardiovascular reactivity can predict hypertension development in African Americans, these findings have not been consistent among all studies examining reactivity and hypertension susceptibility. This inconsistency may be explained by the influence of anxiety (state and trait) on the blood pressure response to stress. Therefore, this study sought to determine whether anxiety is associated with blood pressure response to cold pressor (CP) and anger recall (AR) stress tests in young healthy African Americans. Modeling using state and trait anxiety revealed that state anxiety predicts systolic (SBP) and diastolic blood pressure DBP response to CP and AR (P ≤ 0.02). Interestingly, state anxiety predicted heart rate changes only to CP (P < 0.01; P = 0.3 for AR). Although trait anxiety was associated with SBP response to AR and not CP, it was not a significant predictor of reactivity in our models. We conclude that anxiety levels may contribute to the variable blood pressure response to acute stressors and, therefore, should be assessed when performing cardiovascular reactivity measures.