Mechanisms of endothelin-1 induced reactive oxygen species production in vascular adventitial fibroblasts

With the relationship between endothelin-1 (ET-1) stimulation and reactive oxygen species (ROS) production unknown in adventitial fibroblasts, I examined the ROS response to ET-1 and angiotensin (Ang II). ET-1 -induced ROS peaked following 4 hrs of ET-1 stimulation and was inhibited by an ETA receptor antagonist (BQ 123, 1 uM) an extracellular signal-regulated kinase (ERK) 1/2 inhibitor (PD98059, 10 uM), and by both a specific, apocynin (10 uM), and non-specific, diphenyleneiodonium (10 uM), NAD(P)H oxidase inhibitor. NOX2 knockout fibroblasts did not produce an ET-1 induced change in ROS levels. Ang II treatment increased ROS levels in a biphasic manner, with the second peak occurring 6 hrs following stimulation. The secondary phase of Ang II induced ROS was inhibited by an ATi receptor antagonist, Losartan (100 uM) and BQ 123. In conclusion, ET-1 induces ROS production primarily through an ETA-ERKl/2 NOX2 pathway, additionally, Ang II-induced ROS production also involves an ETa pathway.

Baroreflex sensitivity and developmental coordination disorder

Developmental coordination disorder (DCD) is a motor coordination disorder that is characterized by impairment of motor skills which leads to challenges with performing activities of daily living. Children with DCD have been shown to be less physically active and have increased body fatness. This is an important finding since a sedentary lifestyle and obesity are risk factors for cardiovascular disease. One indicator of cardiovascular health is baroreflex sensitivity (BRS), which is a measure of short term BP regulation that is accomplished through changes in HR. Diminished BRS is predictive of cardiovascular morbidity and mortality. The purpose of this study was to investigate BRS in 117 children aged 12 to 13 years with probable DCD (pOCO) and their matched controls with normal coordination. Following 15 minutes of supine rest, five minutes of continuous beat-by-beat blood pressure (Finapres) and RR interval were recorded (standard ECG). Spectral indices were computed using Fast Fourier Transform and transfer function analysis was used to compute BRS. High frequency and low frequency power spectral areas were set to 0.15-0.6 Hz and 0.04-0.15 Hz, respectively. BRS was compared between groups with an independent t-test and the difference was not significant. It is likely that a difference in BRS was not seen between groups since the difference in BMI between groups was small. As well, differences in BRS may not have manifested yet at this early age. However, the cardiovascular health of this population still deserves attention since differences in body composition and fitness were found between groups.

The form and function of aggressive subtypes: Relations with the goodness of fit between adolescent temperament and parent personality

The current research investigated whether the interaction between adolescent temperament and parent personality, consistent with the goodness of fit perspective, differentially predicted overt (e.g., kicking, punching, insulting) and relational (e.g., gossiping, rumour spreading, ostracising) forms of reactive (e.g., provoked, a response to goal blocking, unplanned and emotional) and proactive (e.g., unprovoked, goal-directed, deliberate and relatively unemotional) aggression. Mothers, fathers and their adolescent child (N = 448, age 10-17) from southern Ontario, Canada filled out questionnaires on adolescent temperament (i.e., frustration, fear, and effortful control) and aggression. Parents reported on their own personality traits (i.e., agreeableness, conscientiousness, and emotional stability). The form and function of aggression not encompassed by the subtype under investigation were controlled in each regression analysis. Consistent with the hypothesis, results indicated that a poor fit between adolescent temperament vulnerabilities and lower parent personality traits, including agreeableness, conscientiousness and emotional stability, was predictive of greater levels of differentiated aggression. For instance, lower father conscientiousness strengthened the relation between higher frustration and reactive overt aggression. Unexpectedly in some cases, temperament risk factors were more strongly associated with aggression subtypes when personality scores were at higher levels, particularly agreeableness and conscientiousness, traits normally considered to be at the optimal end of the dimension. For example, higher father agreeableness strengthened the relation between higher frustration and reactive relational aggression. At the main effects level, low fearfulness was significantly associated with only the overt subtypes of aggression, and unexpectedly, higher frustration and lower effortful control were related to both proactive and reactive subtypes of aggression. A temperamentally vulnerable adolescent was also at greater risk of displaying aggressive behaviour when the father lacked emotional stability, but not the mother. These results are broadly consistent with the prediction that temperament risk factors are more strongly associated with aggression subtypes when an adolescent predisposition does not fit well with parent personality traits. Mechanisms pertaining to stress in the family environment and the fostering of self-regulation abilities are discussed with respect to why a poor fit between temperament and parent personality is predictive of adolescent differentiated aggression.