Abstract: SA-PO0008
Postnephrogenic Angiotensin II Signaling Drives Renal Medullary Microvascular Development and Programs Blood Pressure in Adults
Session Information
- Development, Stem Cells, and Regenerative Medicine
October 24, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Development, Stem Cells, and Regenerative Medicine
- 700 Development, Stem Cells, and Regenerative Medicine
Authors
- Madsen, Kirsten, Syddansk Universitet Det Sundhedsvidenskabelige Fakultet, Odense, Region Syddanmark, Denmark
- Bach, Marie Lykke, Syddansk Universitet Det Sundhedsvidenskabelige Fakultet, Odense, Region Syddanmark, Denmark
- Andersen, Lene Bundgaard, Syddansk Universitet Det Sundhedsvidenskabelige Fakultet, Odense, Region Syddanmark, Denmark
- Jensen, Boye, Syddansk Universitet Det Sundhedsvidenskabelige Fakultet, Odense, Region Syddanmark, Denmark
- Almeida, Lucas, University of Virginia, Charlottesville, Virginia, United States
Background
Adverse events during fetal development can program lifelong vulnerability to hypertension. While reduced nephron number has been emphasized, the contribution of postnatal renal medullary vascular expansion and maturation to long-term blood pressure regulation remains under-explored. We hypothesized that angiotensin II (ANGII)-AT1 receptor signaling is critical for renal medullary microvascular development after nephrogenesis and interruption can lead to long-term dysregulation of blood pressure in adulthood.
Methods
Male and female Sprague-Dawley rat pups were treated with the AT1 receptor blocker candesartan (1 mg/kg/day) at postnatal days P7–P15 and P10–P15 after nephrogenesis has ceased. Cortical and renal medullary microvessels were quantified by unbiased stereology. In a third group of rats treated P7-15, arterial blood pressure was determined in adulthood (P90) by indwelling chronic arterial catheters at baseline and in response to high salt intake.
Results
AT1 receptor blockade during the postnatal window P7–P15, but not P10–P15, impaired selectively renal medullary microvascular development, reducing capillary length, surface area, and volume and increasing diffusion distance while the cortical microvasculature was unaffected. In adult rats (P90), the early structural abnormalities persisted and were associated with impaired urine concentrating capacity while 24h urine albumin, NGAL and aldosterone excretions were not changed. Plasma creatinine and BUN was increased. Adult rats exhibited elevated arterial blood pressure at baseline with a further increase by high-sodium intake. No changes were observed in heart rate. In response to high salt intake, plasma renin and aldosterone were suppressed similarly.
Conclusion
ANGII–AT1 receptor signaling during P7–P15 but not P10-15 is essential for renal medullary microvascular expansion. The permanent disruption of the medullary microvascular structure leads to adult hypertension despite an intact renal cortical morphology suggesting a role in fetal programming of hypertension independent of nephron number.
Acknowledgment
The authors kindly acknowledge laboratory technicians Amalie Kamstrup Mogensen and Jesper Kingo Andresen for excellent technical assistance.
Funding
- Private Foundation Support