Renal proximal tubule angiotensin AT1A receptors regulate blood pressure

Li, Huiping; Weatherford, Eric T.; Davis, Deborah R.; Keen, Henry L.; Grobe, Justin L; Daugherty, Alan; Cassis, Lisa A.; Allen, Andrew M.; Sigmund, Curt D.

doi:10.1152/ajpregu.00124.2011

Cited by 78 publications

(84 citation statements)

References 38 publications

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“…Depletion of endogenous AT 1a receptor in the proximal tubule reduced blood pressure. However, there was no difference in the blood pressure response to a pressor dose of AngII in either experimental model, suggesting that the AT 1a receptor in the renal proximal tubule is a regulator of systemic blood pressure under baseline conditions (Li et al, 2011).…”

Section: Mouse Modelsmentioning

confidence: 75%

International Union of Basic and Clinical Pharmacology. XCIX. Angiotensin Receptors: Interpreters of Pathophysiological Angiotensinergic Stimuli

et al. 2015

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Section: Mouse Modelsmentioning

confidence: 75%

International Union of Basic and Clinical Pharmacology. XCIX. Angiotensin Receptors: Interpreters of Pathophysiological Angiotensinergic Stimuli

et al. 2015

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“…These factors combine to cause marked elevations in fluid delivery to the loops of Henle. Furthermore, long-term activation or inhibition of angiotensin II-mediated transport in the proximal tubule can affect BP, presumably through progressive changes of body Na content (71,108).…”

Section: Proximal Nephronmentioning

confidence: 99%

Integrated Control of Na Transport along the Nephron

Palmer

Schnermann

2015

Clinical Journal of the American Society of Nephrology

189

153

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The kidney filters vast quantities of Na at the glomerulus but excretes a very small fraction of this Na in the final urine. Although almost every nephron segment participates in the reabsorption of Na in the normal kidney, the proximal segments (from the glomerulus to the macula densa) and the distal segments (past the macula densa) play different roles. The proximal tubule and the thick ascending limb of the loop of Henle interact with the filtration apparatus to deliver Na to the distal nephron at a rather constant rate. This involves regulation of both filtration and reabsorption through the processes of glomerulotubular balance and tubuloglomerular feedback. The more distal segments, including the distal convoluted tubule (DCT), connecting tubule, and collecting duct, regulate Na reabsorption to match the excretion with dietary intake. The relative amounts of Na reabsorbed in the DCT, which mainly reabsorbs NaCl, and by more downstream segments that exchange Na for K are variable, allowing the simultaneous regulation of both Na and K excretion.

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“…For example, we and others have shown that AT 1A receptors in the renal proximal tubule play an important role in Ang II-dependent hypertension by augmenting renal sodium reabsorption through activation of key sodium transporter, including NHE3. 6,7 However, eliminating AT 1A receptors in renal epithelia only partially recapitulated the actions of Ang receptor blockers to abrogate hypertension. Along with kidney epithelia, AT 1 receptors are broadly expressed on the renal vasculature.…”

mentioning

confidence: 99%

Vascular Type 1A Angiotensin II Receptors Control BP by Regulating Renal Blood Flow and Urinary Sodium Excretion

Sparks

Stegbauer

Chen

et al. 2015

Journal of the American Society of Nephrology

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Inappropriate activation of the type 1A angiotensin (AT 1A ) receptor contributes to the pathogenesis of hypertension and its associated complications. To define the role for actions of vascular AT 1A receptors in BP regulation and hypertension pathogenesis, we generated mice with cell-specific deletion of AT 1A receptors in smooth muscle cells (SMKO mice) using Loxp technology and Cre transgenes with robust expression in both conductance and resistance arteries. We found that elimination of AT 1A receptors from vascular smooth muscle cells (VSMCs) caused a modest (approximately 7 mmHg) yet significant reduction in baseline BP and exaggerated sodium sensitivity in mice. Additionally, the severity of angiotensin II (Ang II)-dependent hypertension was dramatically attenuated in SMKO mice, and this protection against hypertension was associated with enhanced urinary excretion of sodium. Despite the lower BP, acute vasoconstrictor responses to Ang II in the systemic vasculature were largely preserved (approximately 80% of control levels) in SMKO mice because of exaggerated activity of the sympathetic nervous system rather than residual actions of AT 1B receptors. In contrast, Ang II-dependent responses in the renal circulation were almost completely eliminated in SMKO mice (approximately 5%-10% of control levels). These findings suggest that direct actions of AT 1A receptors in VSMCs are essential for regulation of renal blood flow by Ang II and highlight the capacity of Ang II-dependent vascular responses in the kidney to effect natriuresis and BP control.

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Renal proximal tubule angiotensin AT1A receptors regulate blood pressure

Cited by 78 publications

References 38 publications

International Union of Basic and Clinical Pharmacology. XCIX. Angiotensin Receptors: Interpreters of Pathophysiological Angiotensinergic Stimuli

International Union of Basic and Clinical Pharmacology. XCIX. Angiotensin Receptors: Interpreters of Pathophysiological Angiotensinergic Stimuli

Integrated Control of Na Transport along the Nephron

Vascular Type 1A Angiotensin II Receptors Control BP by Regulating Renal Blood Flow and Urinary Sodium Excretion

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