What role does angiotensin II play in the development of hypertension? This study investigates the complex regulation of intrarenal angiotensin II (Ang II) and its implications for hypertension. The research explores how Ang II, formed from both systemically delivered and intrarenally produced substrate, is compartmentalized within the kidney, significantly exceeding circulating levels in renal interstitial and proximal tubule fluids. In Ang II–dependent hypertension, the study finds that elevated intrarenal Ang II levels persist even when intrarenal renin expression is suppressed. Augmentation of intrarenal Ang II results from the uptake of circulating Ang II via Ang II type 1 (AT1) receptors, coupled with sustained endogenous production. Internalized Ang II accumulates in endosomes, potentially influencing intracellular actions and further upregulating angiotensinogen (AGT) mRNA and protein levels. This comprehensive analysis demonstrates the significant role of intrarenal Ang II in hypertension pathogenesis. The study suggests that urinary AGT excretion rates, related to kidney Ang II content, could serve as an index of Ang II–dependent hypertension. These findings support the development of targeted therapies to manage hypertension by addressing intrarenal Ang II activity.
Hypertension is a leading journal in cardiovascular research. This paper aligns perfectly with the journal’s focus on the mechanisms and treatments of hypertension. By examining the role of intrarenal angiotensin II, the study provides insights that are directly relevant to the journal's audience of researchers and clinicians in the field of hypertension and cardiovascular disease.