Recent experiments using primary culture of rat astrocytes have demonstrated that both the expression and the transport function of P-gp are downregulated following exposure to HIV viral envelope protein, gp120. Collectively, these crucial glial cells that harbour the virus within the CNS are thought to form a dynamic barrier behind the BBB to further impede the access of anti-HIV drugs to sites of infection within the CNS (Ronaldson and Bendayan, 2006). Furthermore, using intact, isolated rat brain capillaries, Hartz et al. (2004) revealed that subnanomolar to nanomolar concentrations of the hormone endothelin-1 (ET-1) rapidly and reversibly attenuated P-gp-mediated transport function over the short term (minutes). This effect was found to be due to the stimulation of the ETB receptor with subsequent activation of nitric oxide synthase and protein kinase C. The release of ET-1 has been apparent in a number of CNS disorders including HIVE (Hartz et al., 2004) and AIDS dementia complex however the effect of ET-1 on brain capillary permeability remains controversial, with some studies claiming that ET-1 significantly increases brain permeability and others suggesting no effect. This discrepancy can be attributed to the different durations of the experiments. An increase in permeability was observed over hours to days, raising the possibility that capillary permeability may remain unchanged during early ET-1 exposure (Hartz et al., 2004).