Intrarenal angiotensin-converting enzyme induces hypertension in response to angiotensin I infusion.
ABSTRACT The contribution of the intrarenal renin-angiotensin system to the development of hypertension is incompletely understood. Here, we used targeted homologous recombination to generate mice that express angiotensin-converting enzyme (ACE) in the kidney tubules but not in other tissues. Mice homozygous for this genetic modification (ACE 9/9 mice) had low BP levels, impaired ability to concentrate urine, and variable medullary thinning. In accord with the ACE distribution, these mice also had reduced circulating angiotensin II and high plasma renin concentration but maintained normal kidney angiotensin II levels. In response to chronic angiotensin I infusions, ACE 9/9 mice displayed increased kidney angiotensin II, enhanced rate of urinary angiotensin II excretion, and development of hypertension. These findings suggest that intrarenal ACE-derived angiotensin II formation, even in the absence of systemic ACE, increases kidney angiotensin II levels and promotes the development of hypertension.
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ABSTRACT: Hypertension is a major risk factor for cardiovascular disease. While the cause of hypertension is multifactorial, renal dysregulation of salt and water excretion is a major factor. All components of the renin-angiotensin system are produced locally in the kidney, suggesting that intrarenal generation of angiotensin II plays a key role in blood pressure regulation. Here, we show that two mouse models lacking renal angiotensin converting enzyme (ACE) are protected against angiotensin II and l-NAME induced hypertension. In response to hypertensive stimuli, mice lacking renal ACE do not produce renal angiotensin II. These studies indicate that the intrarenal renin-angiotensin system works as an entity separate from systemic angiotensin II generation. Renal ACE appears necessary for experimental hypertension. Copyright © 2015 Elsevier Ltd. All rights reserved.Current Opinion in Pharmacology 04/2015; 21. DOI:10.1016/j.coph.2015.01.002 · 4.23 Impact Factor
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ABSTRACT: The kidney continuously adapts daily renal excretion of NaCl to match dietary intakes in order to maintain the NaCl content of the body, and keep vascular volume constant. Any situation that leads to NaCl retention favors a rise in blood pressure. The aldosterone-sensitive distal nephron, which contains two main types of cells, principal (PC) and intercalated (IC) cells, is an important site for the final regulation of urinary Na(+) excretion. Research over the past 20 years established a paradigm in which PCs are the exclusive site of Na(+) absorption while ICs are solely dedicated to acid-base transport. Recent studies have revealed the unexpected importance of ICs for NaCl reabsorption. Here, we review the mechanisms of Na(+) and Cl(-) transport in the aldosterone-sensitive distal nephron, with emphasis on the role of ICs in maintaining NaCl balance and normal blood pressure.Current Hypertension Reports 04/2015; 17(4):538. DOI:10.1007/s11906-015-0538-0 · 3.90 Impact Factor
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ABSTRACT: The physiological hydroelectrolytic balance and the redox steady state in the kidney are accomplished by an intricate interaction between signals from extrarenal and intrarenal sources and between antinatriuretic and natriuretic factors. Angiotensin II, atrial natriuretic peptide and intrarenal dopamine play a pivotal role in this interactive network. The balance between endogenous antioxidant agents like the renal dopaminergic system and atrial natriuretic peptide, by one side, and the prooxidant effect of the renin angiotensin system, by the other side, contributes to ensuring the normal function of the kidney. Different pathological scenarios, as nephrotic syndrome and hypertension, where renal sodium excretion is altered, are associated with an impaired interaction between two natriuretic systems as the renal dopaminergic system and atrial natriuretic peptide that may be involved in the pathogenesis of renal diseases. The aim of this review is to update and comment the most recent evidences about the intracellular pathways involved in the relationship between endogenous antioxidant agents like the renal dopaminergic system and atrial natriuretic peptide and the prooxidant effect of the renin angiotensin system in the pathogenesis of renal inflammation.11/2014; 2014:731350. DOI:10.1155/2014/731350