Renal Pathophysiological Changes During Chronic Metabolic Acidosis Associated Increased Blood Pressure

Abstract

Activation of renal angiotensin II works synergistically with renal superoxides to promote an increase in blood pressure during chronic acidotic conditions has been previously delineated. Uncontrolled high blood pressure instigates renal pathophysiological function and eventual end organ damage is evident. This study aims to investigate the renal consequences of increased blood pressure provoked during chronic metabolic acidosis (CMA). It was a challenging prospect, as both hypertension and chronic metabolic acidosis are two different pathological conditions and can exist independent of each other. Renal functions in rats grouped in 3 groups; i) Control (nonacidotic and normotensive), ii) CMA (acidotic and hypertensive), iii) CMA+captopril+tempol (acidotic and normotensive) were critically assessed by measuring Glomerular Filtration Rate (GFR), Fractional excretion of sodium (FENa), urine flow rate, weight of the kidneys and albuminuria. Picro‐sirius staining of the cortical sections was performed to examine the collagen content as an index of fibrosis. The results demonstrated significant attenuation of GFR in the CMA group compared to the control group. However, GFR in captopril+tempol treated acidotic rats is significantly increased compared to the CMA groups, which suggested that the reduced GFR in CMA group is because the rats are hypertensive. Conversely, the FENa was significantly increased in the CMA group compared to the control but the captopril+tempol treated group showed a significant decrease in FENa compared to the CMA group, this implied that hypertension but not acidosis is the cause of increased FENa which increases blood flow to the kidney potentially leading to the pressure natriuresis and could potentially lead to kidney damage. The urinary albumin excretion was also significantly elevated in acidotic rats as compared to control but the 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 morphological analysis of renal changes using Picro‐sirius staining revealed significant structural damage in the glomeruli of chronically acidotic rats. However, when these rats were treated with captopril and tempol combined, the glomeruli were intact and a reduction in fibrosis was observed. Overall, our results suggested the renal consequences of acidosis induced hypertension can lead to eventual end organ damage which is independent to the function of acidosis. Hence, intrarenal Ang II and superoxide release in the kidney could be a potential target to reduce the blood pressure, albuminuria, and protection of renal function and delayed the onset of end‐stage renal disease associated with acidosis evoked hypertension.