Allen Cowley

..13BN rats in vivo. We conclude that paracrine signaling from mTAL buffers angiotensin II vasoconstriction in Dahl salt-resistant SS.13BN rats but not SS rats...

..We attempted to replicate these findings in an independent sample of 2474 unrelated African Americans in the Milwaukee metropolitan area; 53% were women and 47% were hypertensives...

..BN13 rats. These results reveal a powerful gene, or set of genes, within chromosome 13 of BN/Mcw rats that confers protection from the detrimental effects of high salt to the SS/Mcw rats...

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..The mitochondrial production of H(2)O(2) may represent an important target for development of more effective antioxidant therapies...

..Together with the computational reconstruction of regulatory networks, these methods provide opportunities to significantly advance our understanding of the underlying aetiology of hypertension...

..It is concluded that NO production in the renal medulla plays a very important role in sodium and water homeostasis and the long-term control of arterial pressure...

..Consomic rat strains are proving to be a unique scientific resource that greatly extends our understanding of genes and complex normal and pathological function...

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..The elevated blood flow to the renal cortex may enhance sodium excretion and contribute to long-term sodium homeostasis...

..Given the unlikely chance of these different blood pressure traits mapping to the same region, we believe these data provide evidence that this region of rat chromosome 18 plays an important role in salt-induced hypertension...

..is primarily produced in the renal OM; (2) both NADH oxidase and mitochondrial enzymes are responsible for the O(2)(-.)production in this kidney region; and (3) O(2)(-. )exerts a tonic regulatory action on renal MBF...

..3 microg/kg per minute). This study demonstrates that AVP increases renal medullary interstitial [NO] through vasopressin V2 receptor stimulation, which in turn elevates blood flow to the renal medulla...

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..Several chromosomal substitutions slightly altered the ventilatory responses to hypoxia and exercise. However, genes on chromosomes 6 and Y of those studied are of primary importance in aspects of ventilatory control currently studied...

..These changes are essential to provide a constancy of blood flow to the renal medulla and buffer against the hypertensive actions of this potent vasoconstrictor peptide...

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..Plasma hormone levels in both groups of PHD studied responded in a manner similar to normal mongrel dogs with reductions of PRA, ALDO, elevations of ANP, and no change in AVP.(ABSTRACT TRUNCATED AT 250 WORDS)..

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..The present data are consistent with the idea that chronic stimulation of V2 receptors by AVP offsets the vasoconstrictor and hypertension actions of AVP-induced stimulation of medullary V1 receptors...

..The results provide novel insights of how the organism attempts to protect itself from the hypertensive effects of Ang II...

..The data show that stimulation of adenosine production and downregulation of A1 receptors with salt loading may play an important role in adaptation in the kidney to promote sodium excretion...

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..5. The data reviewed indicate that NO in the renal medulla has a powerful influence on fluid and electrolyte homeostasis and the control of blood pressure...

..Body weight increased throughout the study but was unrelated to the changes of MAP. We conclude that chronic stimulation of V1 receptors results in sustained hypertension in rats...

..Evidence for AT2R mRNA was also found in all but two of the vascular and tubular segments, the MTAL, and the glomeruli. These results are consistent with the whole tissue immunohistochemically localized receptors...

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..It is concluded that HIF-1-mediated molecular adaptation to low PO2 is of importance in the regulation of renal medullary function and that ROS may target this HIF-1-mediated medullary adaptation to damage renal function...

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..Consomic rat strains are proving to be a unique scientific resource that can greatly extend our understanding of genes and their role in the regulation of complex function and disease...

..In summary, this study demonstrates that elevated RPP is directly responsible for the excess albuminuria in Ang II-infused rats, whereas both elevated RPP and Ang II directly contribute to the observed renal oxidative stress...

..Because the BN chromosome is removed from its native background and the SS rat loses a native chromosome, it is also necessary to consider the contribution of changes in gene-to-gene interaction...

..This may lead to reduction in medullary blood flow and promote hypoxia and tubular necrosis within the renal medulla during in hypertension...

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..We conclude that excess renal medullary superoxide production in SS rats contributes to salt-induced hypertension, and NADPH oxidase is the major source of the excess superoxide...

..We conclude that oxidative stress within the renal medulla can induce hypertension and also make the kidney functionally more vulnerable to the effects of Ang II...

..These data provide a baseline for physiological comparison of traits related to cardiovascular, lung, blood, and renal function in the sequenced BN rats relative to the major strains of rats studied in biomedical research...

..These data show that medullary production of H2O2 may contribute to salt-induced hypertension in SS rats and that chromosome 13 of the Brown Norway contains gene(s) that protect against renal medullary oxidant stress...

..Based on the shift of BH(4) to BH(2) and the observation of l-NAME inhibitable superoxide production, we conclude that NOS uncoupling occurs in the renal medulla of hypertensive SS rats fed a high-salt diet...

..Amiloride-sensitive O(2)(-) production is likely to contribute to augmented outer medullary O(2)(-) production observed in SS rats during both normal and high NaCl diets...

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..We conclude that elevations of RPP contribute significantly to the fibrosis and epithelial-to-mesenchymal transition found in the early phases of hypertension in the salt-sensitive rat...

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..Many of these would have been missed in a traditional, sex-adjusted setting...

..The present data indicate that genes that can modify l-NAME-induced hypertension and proteinuria are on chromosomes 1, 15, 16, 18, and 20...

..We conclude from these studies that there are four regions within chromosome 13 containing genes that interact epistatically and influence arterial pressure...

..We conclude that AVP-induced NO production in IMCD is dependent on V2R activation of the phosphoinositide pathway and the mobilization of Ca(2+) from both intracellular and extracellular pools...

..Diffusion of O(2)(*-) from mTAL to surrounding tissue could contribute to reduced bioavailability of NO, reductions of medullary blood flow, and interstitial fibrosis in the outer medulla of SS/Mcwi rats...

..Thus lentiviral transgenesis provides a powerful tool for the production of transgenic inbred rats and will enhance the usefulness of this species in gene discovery and target validation studies...

..Furthermore, this consomic rat panel provides a stable genetic platform that can facilitate further gene mapping by either linkage studies or the breeding of congenic and subcongenic rats...

..These observations are consistent with the hypothesis that aldosterone-induced volume expansion is an important contributor to hypertension, especially in blacks...

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..We conclude that AngII stimulates O2*- production in mTAL via the NAD(P)H oxidase pathway and that interactions of O2*- and NO ultimately determine the effectiveness of in situ free-radical cross-talk between the mTAL and the VR...

..These results indicate that an impaired NO counterregulatory system in the outer medulla of Dahl S rats makes them more susceptible to the hypertensive actions of small elevations of ANG II...

..We conclude that Ang II increases [Ca2+]i in pericytes of the descending vasa recta as part of its constrictor action and that this vasoconstriction is buffered by the NO from the surrounding tubular elements, such as mTALs...

..Focusing on hypertension-related phenotypes is a promising approach for identifying the genetic determinants of hypertension...

..Recommendations regarding the use of these procedures were proposed...

..This counteracting effect of H2O2 may limit the use of tempol as an antihypertensive agent under exaggerated oxidative stress in the kidney...

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..The development of a female rat systems biology map of cardiovascular function represents the first attempt to prioritize those regions of the genome important for development of hypertension and end organ damage in female rats...

..These data demonstrate a significant influence of diet composition on salt-induced hypertension and renal disease in the Dahl SS/Mcw rat...

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..These results should provide an informative source for designing future functional studies in salt-sensitive hypertension...

..Qualitatively similar results were obtained from female FHH, FHH-1BN, and BN rats. The present results indicate that genes contributing to l-NAME-induced hypertension and renal disease are found on chromosome 1 of the FHH rat...

..We conclude that AVP mobilizes Ca(2+) to produce NO in IMCDs...

..In summary, genes with known inflammatory, remodeling, and vasoactive activities were identified in rat kidneys after recovery from ARF, some of which may play a role in altering long-term renal function after recovery from ARF...

..We conclude that the preferential juxtamedullary injury found in Ang II hypertension is largely induced by pressure and is probably mediated through the TGF-beta and NF-kappaB pathway...

..The present experiments indicate that an increase in superoxide concentration within the renal medulla selectively reduces medullary blood flow resulting in chronic hypertension...

..We conclude that elevations of extracellular NaCl, D-glucose, or T3 levels can activate both the Na+/K+-ATPase pump and Na+/H+ exchanger in mTAL, which, in turn, is associated with increased intracellular concentrations of superoxide...

..With a keen sense of homeostasis, global regulation, and quantitative analysis, integrative physiologists are uniquely positioned to apply these techniques to enhance the understanding of complex physiological functions...

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..The previously unimaginable goal of connecting approximately 36,000 genes to the complex functions of mammalian systems is indeed well underway...

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..These results suggest that investigating clinically defined subtypes of hypertension, such as obesity-associated hypertension, may facilitate the search for genes of this complex disorder...

..An understanding of these mechanisms could lead to new therapeutic approaches for the prevention of kidney disease in hypertension. ..

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..An understanding of these mechanisms could lead to new therapeutic approaches for the prevention of kidney disease in hypertension. ..

..The four Cores that will provide support for the PPG include: A) Administrative Core; B) Genomics Core; C) Transgenics Core; D) Research Services Core. ..

..We are encouraged by the success of the training program thus far and the number of high quality applicants in our pools, so we are therefore requesting that the number of slots be increased from five to nine. ..

..To develop a compelling set of recommendations for research initiatives in TMJDs that would synergize the work of multiple Institutes and Centers of the National Institutes of Health and that of academic health centers. ..

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