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Angiotensin II (ANG II) and its receptors, AT1 and AT2, may modulate kidney development. To define the temporal and spatial distribution of AT1 and AT2 receptors and their mRNAs during nephrogenesis, fetal, newborn, and adult rat kidneys were studied using reverse transcription-polymerase chain reaction and radioligand binding autoradiography. AT1 expression was minimal at embryonic day 14 (E14), highly expressed at E20, and persisted into adulthood. Conversely, AT2 expression was easily detected from E14 through postnatal day 7 but was undetectable by postnatal day 28. At E14, 76% of the receptors were AT2, 24% were AT1, and both were found in the undifferentiated mesenchyme. By E17, AT1 comprised 40% of the receptors and localized to mature nephron segments, whereas AT2 remained within both condensed mesenchyme and differentiating epithelia. The dissociation constants for AT1 and AT2 were 0.45 +/- 0.09 nM and 0.73 +/- 0.15 nM, respectively, at E17, similar to adult values. By E20, AT1 and AT2 colocalized to the outer medullary stripe, deep nephrons, medullary rays, and blood vessels, while AT2 continued to predominate in the actively differentiating cortex. The presence of both subtypes of receptors capable of binding ANG II during early nephrogenesis and the time-dependent and structure-specific regulation of receptor localization confirm a regulated developmental program for receptor expression and suggest important roles for AT1 and AT2 in renal morphogenesis.

Infection of biomaterial implants is an expensive and devastating complication of orthopaedic surgery historically ranging from less than 1% in primary total knee arthroplasty (TKA) to 10% in revision TKA. An in vivo animal model was developed to test the efficacy of innovative therapies for the prevention of biomaterial centered infections caused by methicillin-resistant Staphylococcus aureus bacteria (MRSA). Twenty-two New Zealand White rabbits were used in this study. After proper anesthesia, a stainless-steel screw with a high molecular weight polyethylene (UHMWPE) washer was cemented in a defect created in the intra-articular, nonarticulating portion of the lateral femoral condyle of each knee. After closure of the joint capsule, each knee was inoculated with 0, lo2, lo', or lo4 colony forming units (CFU) of MRSA. Animals were sacrificed after 7 days at which time joint aspirate, tissues and biomaterial samples were examined for evidence of infection.A total of 42 knees were used for analysis. When saline was injected into the knee, 0/10 of the knees demonstrated evidence of biomaterial centered infection (with the contralateral knee receiving lo4 CFU MRSA). Four of 10 knees developed a biomaterial centered infection when lo2 CFU MRSA was introduced. Seven out of 10 knees developed a biomaterial centered infection when either lo3 or lo4 CFU MRSA was injected. No evidence of septicemia (positive blood cultures) was found in any animal. This rabbit knee model utilizes commonly employed inexpensive orthopaedic implant materials in an in vivo milieu and provides an effective method for the evaluation of treatments for biomaterial centered infections.

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