The addition of VU573 to the peritubular bath significantly inhibits the rate of fluid secretion to 0.26 nl/min after 2 hours, AMG 548 whereas the addition of the vehicle or VU342 has no effect on the rate of fluid secretion after 2 hours. Thus, VU573 inhibits the first step in urine formation at the level of the Malpighian tubules. To confirm the inhibition of Kir channels by VU573, we used two-electrode voltage clamping to measure the basolateral membrane voltage and input resistance of principal cells of isolated Malpighian tubules. Peritubular application of VU573 significantly hyperpolarizes the Vbl by 7.0 mV while increasing the Rpc by 5.7 kV ; these changes are consistent with the blockade of Kir channels in the basolateral membrane of Malpighian tubules. By comparison, peritubular application of barium at 5 mM, which is a generic Cardionogen 1 blocker of potassium channels including Kir channels, also significantly hyperpolarizes the Vbl while increasing the Rpc. The channel block by Ba2+ is significantly greater than that of VU573, which is to be expected given that it is less selective than VU573. To determine whether the VU573-mediated inhibition of fluid secretion by isolated Malpighian tubules causes renal failure in intact mosquitoes, we measured urine excretion rates using a method modified from the laboratory of Hansen. Mosquitoes fed on a sucrose solution ad libitum excrete urine at a rate of 0.41 nl/min, whereas those injected with 900 nl of a Na + -HEPES-buffered saline ��a volume 30% less than that ingested with a blood meal ��excrete urine at a significantly higher rate of 5.64 nl/min. The rate of urine excretion is significantly dampened to 2.14 nl/min if the Na + -HBS contains VU573, whereas the rate is unaffected if the Na + -HBS contains VU342. In conclusion, we have demonstrated that a small-molecule inhibitor of Kir channels elicits renal failure in female mosquitoes, which would decrease their reproductive output and ability to transmit pathogens by limiting the number of vertebrate blood meals they could consume. Therefore, such inhibitors could be considered as a potential new class of insecticides to be further developed for combatting the emerging problem of insecticide resistance in mosquitoes. The challenges that lay ahead are the development of: 1) small molecules that inhibit Kir channels of mosquitoes with greater potency than those of humans and beneficial insects, and 2) an efficient and effective system to deliver the inhibitors to mosquitoes. The high-throughput screening assay for AeKir1 established in the present study will expedite the former effort. While highly active antiretroviral therapy has reduced mortality related to infectious complications in people with HIV, they are more likely than HIV-uninfected persons to have subclinical cardiovascular disease or be diagnosed with myocardial infarction, congestive heart failure, cardiomyopathy, pulmonary hypertension, and chronic obstructive pulmonary disease. Additionally, HAART may play a role in the development of cardiovascular disease.