Background-Angiotensin II (Ang II) plays a critical role in the development of vascular lesions in hypertension, atherosclerosis, and several renal diseases. Because Ang II may contribute to the leukocyte recruitment associated with these pathological states, the aim of the present study was to assess the role of Ang II in leukocyte-endothelial cell interactions in vivo. Methods and Results-Intravital microscopy of the rat mesenteric postcapillary venules was used. Sixty minutes of superfusion with 1 nmol/L Ang II induced a significant increase in leukocyte rolling flux (83.8Ϯ20.7 versus 16.4Ϯ3.1 cells/min), adhesion (11.4Ϯ1.0 versus 0.8Ϯ0.5 cells/100 m), and emigration (4.0Ϯ0.7 versus 0.2Ϯ0.2 cells/field) without any vasoconstrictor activity. These effects were not mediated by mast cell activation. Intravenous pretreatment with AT 1 (losartan) or AT 2 (PD123,319) receptor antagonists significantly reduced Ang II-induced responses. A combination of both receptor antagonists inhibited the leukocyte rolling flux, adhesion, and extravasation elicited by Ang II at 60 minutes. Pretreatment of animals with fucoidin or an adhesion-blocking anti-rat P-selectin monoclonal antibody abolished Ang II-induced leukocyte responses. Furthermore, rat platelet P-selectin expression was not affected by Ang II stimulation. Conclusions-Ang II induces significant leukocyte rolling, adhesion, and emigration, which may contribute not only to hypertension but also to the onset and progression of the vascular damage associated with disease states in which plasma levels of this peptide are elevated.

The NNRTI efavirenz has long been one of the most frequently employed antiretroviral drugs in the multidrug regimens used to treat HIV infection, in accordance with its well-demonstrated antiretroviral efficacy and favourable pharmacokinetics. However, growing concern about its adverse effects has sometimes led to efavirenz being replaced by other drugs in the initial treatment selection or to switching of therapy to efavirenz-free regimens in experienced patients. Neurological and neuropsychiatric reactions are the manifestations most frequently experienced by efavirenz-treated patients and range from transitory effects, such as nightmares, dizziness, insomnia, nervousness and lack of concentration, to more severe symptoms including depression, suicidal ideation or even psychosis. In addition, efavirenz has recently been associated with mild/moderate neurocognitive impairment, which is of specific relevance given that half of the patients receiving ART eventually suffer some form of HIV-associated neurocognitive disorder. The mechanisms responsible for efavirenz-induced neurotoxicity are unclear, although growing evidence points to disturbances in brain mitochondrial function and bioenergetics. This review offers a comprehensive overview of the current evidence on the interaction that efavirenz displays with the CNS, including the penetration and concentration of the drug in the brain. We discuss the prevalence, types and specificities of its side effects and recently uncovered cellular mechanisms that may be involved in their development.