Evidence Linking Alterations in the Moment-to-Moment Pressure-Natriuresis Mechanism to Hypertension and Salt-Sensitivity in Rodents
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Hypertension and salt-sensitivity are independent risk factors for cardiovascular disease. Although both conditions are idiopathic, they develop due to a complex interplay between susceptibility genes and environmental factors. Given that the kidney plays an important role in regulating blood pressure, in particular, by maintaining sodium and water balance via pressure-natriuresis, it is not surprising that disturbances in the proper functioning of this intrarenal mechanism have been linked to these conditions. Although direct coupling of changes in renal arterial pressure (RAP) to renal interstitial hydrostatic pressure (RIHP) and consequent sodium excretion is well established, few studies have characterized the moment-to-moment aspects of this process. Thus, the main focus of the research presented herein was to characterize the moment-to-moment RAP-RIHP relationship, and assess the functioning of this intrarenal mechanism in various animal models of genetic and environmentally-induced hypertension and/or salt-sensitivity. In adult normotensive rats, the response time of RIHP to acute changes in RAP was rapid (<2 seconds), and the moment-to-moment RAP-RIHP relationship was linear over a wide range of pressures. Additionally, the functioning of this relationship was not affected by inhibition of the renin-angiotensin system and autonomic nervous system. Further, the acute RAP-RIHP relationship was impaired in hypertension and/or salt-sensitivity. Specifically, animals with a hypertensive phenotype (i.e. young spontaneously hypertensive rats [SHR] and pro-atrial natriuretic peptide gene-disrupted mice [ANP -/-]) displayed a rightward shift in the moment-to-moment pressure-natriuresis curve towards higher RAP. This rightward shift was associated with increased structurally-based vascular resistance properties in the hindlimb of young SHR versus their normotensive controls. Salt-sensitive phenotypes were associated with a blunting of this acute mechanism. Specifically, this blunting was evident in both the ANP -/-, a transgenic model of salt-sensitive hypertension, and in adult perinatal iron deficient (PID) rats, a developmentally programmed model of salt-sensitivity. It appears that a blunting in the RAP-RIHP relationship is influenced by an imbalance of key blood pressure modulating factors (e.g. ANP). Further, visceral obesity was associated with salt-sensitivity in PID rats; however the mechanism(s) are yet to be elucidated. Novel methodologies (MRI, abdominal girth) were developed for non-invasive assessment of visceral obesity to aid future research.
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