DEFICIENCY OF THE COMPLEMENT RECEPTOR C5AR2 HAS NO EFFECT ON BLOOD PRESSURE AND END ORGAN DAMAGE IN ANGIOTENSIN II INDUCED HYPERTENSION

Objective: Complement activation plays an important role in development of hypertension and hypertensive end organ damage by affecting immunity and tissue integrity. The anaphylatoxin C5a, a key inflammatory mediator of the complement system, binds to the anaphylatoxin receptors C5aR1 and C5aR2. Recently we and others could demonstrate that C5aR1 knockout mice show reduced hypertensive renal end organ damage. However, the role of C5aR2 in hypertension remains unclear. Design and method: First, we investigated the expression of C5aR2 on infiltrating and resident renal and cardiac cells, using a tandem dye (td) tomato-C5aR2 knock-in reporter mouse. Flow cytometry analysis of leukocytes isolated from the kidneys of td tomato-C5aR2 reporter mice showed that dendritic cells were the major population expressing C5aR2 (34%), followed by monocytes/macrophages (30%) and neutrophils (14%). Confocal microscopy did not detect expression of C5aR2 in resident renal or cardiac cells. Results: Next, we examined the influence of C5aR2 deficiency on Ang II-induced hypertension and hypertensive end organ damage. To assess the role of C5aR2 deficiency in hypertensive injury, we used an aggravated model of hypertension including unilateral nephrectomy followed by infusion of Angiotensin (Ang) II (0.75 ng/g/min) and a high salt diet in both wildtype (n=12) and C5aR2 knockout mice (n=18). 9 normotensive mice served as controls. No significant differences were observed regarding blood pressure, renal injury (albuminuria, glomerular filtration rate, glomerular and tubulointerstitial injury, inflammation), or cardiac injury (cardiac fibrosis, heart weight, gene expression) between hypertensive wildtype and hypertensive C5aR2-deficient mice. Conclusions: In summary, our findings showed that while C5aR2 is predominantly expressed on myeloid cells in the kidney, its deficiency does not appear to have an impact on Ang II-induced hypertensive injury.