VCOM Louisiana Research Day Program Book 2024

Biomedical Research: Section 1

Dan Luu, OMS-II; Keith Jackson, PhD; Dinesh Aryal, PhD VCOM-Louisiana; ULM College of Pharmacy 1 ASSESSMENT OF RENAL CHANGES DURING METABOLIC ACIDOSIS PROMOTED HYPERTENSION

Background: Chronic metabolic acidosis (CMA) evoked hypertension has been recently delineated in experimental rats. The synergistic effect of intrarenal angiotensin II (Ang II) and superoxide (a free radical component) has been depicted as a cause of the observed hypertension. Therefore, treating acidotic rats with captopril (ACE inhibitor) and tempol (superoxide scavenger) in combination has shown to be effective in controlling high blood pressure. In the present study we investigate the magnitude of renal changes that occurred during acidotic, acidotic hypertensive and acidotic normotensive states in rats. Objective: To evaluate the magnitude of renal changes occurred during chronic acidosis elicited hypertension compared to acidotic normotensive conditions. Methods: Male Sprague Dawley rats (100-150 g) were divided into three groups: (i) Control (ii) CMA (acidotic), (iii) CMA+captopril+tempol. CMA was induced by providing a weak acid solution of 0.28 M ammonium chloride in drinking water for 8 weeks. Blood pH was measured to confirm rats were acidotic, while blood pressure was monitored weekly using tail-cuff. Urine samples were collected to measure creatinine, albumin-urea, sodium and potassium levels.

Glomerular filtration rate (GFR) was analyzed among all three groups. Further, urine NGAL level was analyzed to assess the kidney injury. Hematoxylin and eosin (H&E) staining were used to verify histological details in the cortical kidney sections. Results: Results demonstrated a significant decline in GFR in the CMA rats vs control group. However, GFR in CMA+captopril+tempol treated acidotic rats is significantly increased vs CMA rats, which suggested that the reduced GFR in CMA group is because the rats are hypertensive. Conversely, the urinary albumin excretion was significantly elevated in acidotic rats but the CMA+captopril+tempol treated group showed a significant reduction in albuminuria, which revealed the acidosis-induced hypertension is contributing for impaired renal infiltration and augmenting the albuminuria. The NGAL levels were significantly increased in CMA rats but declined in CMA+captopril+tempol treated group. The H&E staining revealed significant structural changes with signs of dilated tubular lumina, cellular detachment, and an absence of nuclei indicating tubular necrosis in CMA rats. However, when these rats were treated with captopril and tempol combined, the glomeruli were intact, and nuclei were seen evenly distributed.

Conclusions: Overall, our results suggested the renal consequences of acidosis induced hypertension can lead to eventual kidney injury which is independent of the function of acidosis. Moreover, intrarenal Ang II and superoxide release in the kidney could be a potential target to prevent or treat acute kidney injury (AKI) and its further progression. Further studies are needed to examine if Ang II and superoxide directly affect the renal blood flow during the pathological acute renal injury.

13 2024 Via Research Recognition Day