Air pollution and blood pressure dipping (page 1061)
The documented association of air pollution with increased cardiovascular morbidity and mortality appears to be partly mediated by increased blood pressure. In this issue of Hypertension, Tsai et al report on a study conducted in 359 adults from Lausanne (Switzerland), a city characterized by low average air pollution levels. They found that short-term exposure (ie, 0 to 7 days) to particulate matter with diameter ≤10 µm was associated with higher nighttime blood pressure and reduced nocturnal systolic dipping. So far, little data exist on the association of short-term exposure to particulate matter with circadian rhythm of blood pressure.
This association of particulate matter with blunted blood pressure dipping was preceded by an association with reduced daytime, as well as day-to-night ratio of, renal sodium excretion. This suggests a key role of the kidney via enhanced pressure-natriuresis at night. Although the data are cross-sectional, which limits causal inference, and the effect sizes are small (ie, 1 mm Hg per 10 µg/m3 of particulate matter), these results bring a new possible mechanism underlying a substantial public health problem. Ambulatory monitoring may be useful in hypertensive patients living in highly polluted area. Experimental studies are needed to explore whether reduced exposure to particulate matter can restore nondipping. If this is the case, even modest reductions in air pollution levels could potentially lower cardiovascular risk at the population level because everyone is exposed to air pollution on a daily basis.
Features of childhood hypertension (page 1047)
Current consensus guidelines for evaluation of children and adolescents with confirmed hypertension recommend a full evaluation for secondary causes in younger children, but there is not much evidence in the literature to support these recommendations. What evidence that is available primarily comes from single-center studies of children referred to tertiary centers. In this issue of Hypertension, Flynn and colleagues present their findings from an analysis of baseline data from two pediatric trials of valsartan conducted at multiple centers in the mid-2000s. They show that children <6 years old were significantly more likely to have secondary hypertension than older children (Figure) and that young children had significantly lower estimated glomerular filtration rate than older children, which is consistent with a high prevalence of underlying kidney disease in children <6 years old. Several findings in this report highlight the effects of the obesity epidemic on the epidemiology of pediatric hypertension, including a >50% prevalence of obesity in hypertensive children >6 years old, and evidence of dyslipidemia and hyperfiltration in obese hypertensive patients. Finally, this study shows that diastolic hypertension was more common in young children, whereas children >6 years old were more likely to have isolated systolic hypertension. These data provide robust evidence to support current clinical guidelines for evaluation of hypertensive children, and provide new insights for design of future clinical trials of antihypertensive agents in the pediatric age group.
α2δ-1 induced vasoconstriction in hypertension (page 1006)
A hallmark of hypertension is an elevation in arterial contractility that increases systemic blood pressure and restricts organ blood flow, leading to end-organ damage. Hypertension is also a major predictor for a variety of cerebral diseases, including stroke, Alzheimer disease, and dementia. One pathological alteration that occurs in hypertension is an elevation in vascular smooth muscle cell (myocyte) voltage-dependent Ca2+ influx. Voltage-dependent L-type (Cav1.2) channels are the primary Ca2+ entry pathway in arterial myocytes. A hypertension-associated elevation in myocyte Cav1.2 current leads to an increase in intracellular Ca2+ concentration and vasoconstriction. Voltage-dependent Ca2+ channel blockers have been used for over two decades to treat hypertension. However, Ca2+ channel blockers inhibit Cav1.2 channels in multiple cell types in vivo and produce side effects, including sweating, edema, and nausea. Therefore, the development of alternative approaches to target Cav1.2 channels in arterial myocytes could provide significant benefits over current inhibitors.
Molecular mechanisms that elevate arterial myocyte Cav1.2 currents in hypertension were unclear. Recently, α2δ-1 was identified as being important for functional plasma membrane trafficking of Cav1.2 subunits in arterial myocytes. Here, we show that genetic hypertension in rats is associated with an increase in α2δ-1 expression that elevates plasma membrane Cav1.2 currents in cerebral artery myocytes, leading to vasoconstriction. Our study also demonstrates that α2δ-1 targeting can reverse pathological vasoconstriction and induce cerebrovascular dilation in hypertension. In summary, data in this study suggest that α2δ-1 may be a viable molecular target for antihypertensive therapy.
- © 2012 American Heart Association, Inc.