Exaggerated natriuresis in transgenic (mRen2)27 rats

Area of Science:

• Nephrology
• Cardiovascular Physiology
• Renal Pathophysiology

Background:

• Hypertension is characterized by exaggerated natriuresis following acute volume expansion.
• In humans, the extent of exaggerated natriuresis correlates inversely with angiotensin II levels.

Purpose of the Study:

• To investigate the relationship between exaggerated natriuresis and angiotensin II levels.
• To compare natriuretic responses in transgenic rats (TGR) with an extra renin gene and desoxycorticosterone acetate (DOCA)-salt rats against Sprague-Dawley Hannover (SDH) controls.

Main Methods:

• Uninephrectomized rats (TGR, DOCA-salt, SDH) were instrumented for renal sympathetic nerve activity (RSNA) and renal blood flow (RBF) measurements.
• Glomerular filtration rate (GFR), diuresis, and natriuresis were assessed after saline volume expansion.
• Kidney histology was examined post-experiment.

Main Results:

• TGR and DOCA-salt rats exhibited higher blood pressure and greater diuresis/natriuresis than SDH rats post-volume expansion.
• Cortical RBF was preserved in TGR and DOCA-salt rats, while medullary RBF increased; SDH rats showed decreased cortical RBF.
• RSNA decreased in all groups, but less so in TGR and DOCA-salt rats compared to SDH rats.

Conclusions:

• Exaggerated natriuresis in hypertensive rats occurs independently of angiotensin II levels.
• Both hypertensive rat models demonstrated reduced RSNA response and maintained cortical RBF during volume expansion.
• Findings do not support the hypothesis that exaggerated natriuresis is solely a function of renin-level suppression in rats.