Neurovascular Coupling in Hypertension Is Impaired by IL-17A through Oxidative Stress

Hypertension, a multifactorial chronic inflammatory condition, is an important risk factor for neurovascular and neurodegenerative diseases, including stroke and Alzheimer’s disease. These diseases have been associated with higher concentrations of circulating interleukin (IL)-17A. However, the possible role that IL-17A plays in linking hypertension with neurodegenerative diseases remains to be established. Cerebral blood flow regulation may be the crossroads of these conditions because regulating mechanisms may be altered in hypertension, including neurovascular coupling (NVC), known to participate in the pathogenesis of stroke and Alzheimer’s disease. In the present study, the role of IL-17A on NVC impairment induced by angiotensin (Ang) II in the context of hypertension was examined. Neutralization of IL-17A or specific inhibition of its receptor prevents the NVC impairment (p p p < 0.05) and increases superoxide anion production. Both effects were prevented with Tempol and NADPH oxidase 2 gene deletion. These findings suggest that IL-17A, through superoxide anion production, is an important mediator of cerebrovascular dysregulation induced by Ang II. This pathway is thus a putative therapeutic target to restore cerebrovascular regulation in hypertension

Optical imaging of resting-state functional connectivity in a novel arterial stiffness model

This study aims to assess the impact of unilateral increases in carotid stiffness on cortical functional connectivity measures in the resting state. Using a novel animal model of induced arterial stiffness combined with optical intrinsic signals and laser speckle imaging, resting state functional networks derived from hemodynamic signals are investigated for their modulation by isolated changes in stiffness of the right common carotid artery. By means of seed-based analysis, results showed a decreasing trend of homologous correlation in the motor and cingulate cortices. Furthermore, a graph analysis indicated a randomization of the cortex functional networks, suggesting a loss of connectivity, more specifically in the motor cortex lateral to the treated carotid, which however did not translate in differentiated metabolic activity

Protective Effects of Aspirin from Cardiac Hypertrophy and Oxidative Stress in Cardiomyopathic Hamsters

Objective. To evaluate the capacity of chronic ASA therapy to prevent cardiac alterations and increased oxidative stress in cardiomyopathic hamsters. Methods and Results. Male Syrian cardiomyopathic and age-matched inbred control hamsters received ASA orally from the age of 60 days. Animals were sacrificed at the age of 150, 250, and 350 days to evaluate the time course of cardiac hypertrophy and cardiovascular tissue superoxide anion (O2-) production. At the age of 150 days, the ventricular weight over body weight ratio, resting heart rate, and cardiovascular O2- production were much higher in cardiomyopathic hamsters than those in control. At the age of 250 days, in addition to the continual deterioration of these parameters with age, the blood pressure started to fall and the signs of heart failure appeared. In these cardiomyopathic hamsters, chronic ASA treatment (a) completely prevented elevated O2- production and the NAD(P)H oxidase activity, (b) significantly slowed down the development of the cardiac hypertrophy and fibrosis. Conclusions. Chronic ASA treatment significantly prevents the deterioration of cardiac function and structure as well as the increased oxidative stress in the cardiomyopathic hamster. Our findings suggest that ASA presents a therapeutic potential to prevent cardiac dysfunction

Impact of Sex and Antihypertensive Medication on Global Cognition in Primary Care Older Adults

Hypertension is one of the strongest modifiable risk factors for the development of cognitive impairment and dementia. However, there are conflicting reports regarding which class of antihypertensive medication is the best for reducing the risk of cognitive decline. The objective of this study is to determine whether sex determines the pharmacological therapy that is the most effective in preserving cognitive outcomes. This study examined 1607 participants from the ESA Services Study, a longitudinal survey of older adults over 65 years old in Quebec-Canada. They were examined for the Mini-Mental State Examination(MMSE) at baseline (T1) and followed up three (T2) and four years after (T3). Hypertensive women had the highest mean MMSE score at each time point (T1 28.591 (SE .064); T2 28.282 (SE .118); T3 28.524 (SE.119)), while hypertensive men had the worst (T1 28.038(SE.070); T2 27.694(SE.125); 27.809(SE.128)). Women taking angiotensin II receptor antagonists (ARBs) showed the highest MMSE scores (p<.003), and men taking diuretics and other antihypertensives had the lowest MMSE scores(p<.001) after a 3-year follow-up. Combination therapy of two or three antihypertensives drugs was associated with higher scores in women at T1 and T2 (p<.001). In men, taking three antihypertensives showed a sharp decrease in MMSE scores from T1 to T3 (p<.001). Sex differences in global cognition outcomes in older adults are in part due to the heterogeneity in effects related to the type and number of antihypertensive drugs used. Effective antihypertensive treatment should consider the impact of sex to optimize the effect of pharmacological interventions on cognition

Regulation of intracerebral arteriolar tone by Kv channels: Effects of glucose and PKC

Voltage-gated potassium (K(v)) channels in vascular smooth muscle cells (VSMC) are critical regulators of membrane potential and vascular tone. These channels exert a hyperpolarizing influence to counteract the depolarizing effects of intraluminal pressure and vasoconstrictors. However, the contribution of K(v) channel activity to the functional regulation of cerebral (parenchymal) arterioles within the brain is not known. Thus K(v) channel properties in parenchymal arteriolar SMCs were characterized. Isolated, pressurized parenchymal arterioles and arterioles in cortical brain slices exhibited robust constriction in the presence of the K(v) channel inhibitor 4-aminopyridine (4-AP). 4-AP also decreased the amplitude of K(v) currents recorded from SMCs. The steady-state activation and inactivation properties of K(v) currents suggested that these channels are composed of K(v)1.2 and 1.5 subunits, which was confirmed by RT-PCR. K(v) channels can be regulated by extracellular glucose, which may be involved in the functional hyperemic response in the brain. Thus the effects of glucose on K(v) channel activity and arteriolar function were investigated. Elevation of glucose from 4 to 14 mM significantly decreased the peak K(v) current amplitude and constricted arterioles. Arteriolar constriction was prevented by inhibition of protein kinase C (PKC), consistent with previous studies showing enhanced PKC activity in the presence of elevated glucose. In cortical brain slices, the dilation generated by neuronal activity induced by electrical field stimulation was decreased by 54% in 14 mM glucose when compared with the dilation in 4 mM glucose. In anesthetized mice the whisker stimulation-induced increase in local cerebral blood flow was also significantly decreased in 14 mM glucose, and this effect was similarly prevented by PKC inhibition. These findings point to a critical role for K(v) channels in the regulation of intracerebral arteriolar function and suggest that changes in perivascular glucose levels could directly alter vascular diameter resulting in a modulation of local cerebral blood flow