Interferon alpha/beta receptor 1 inhibition results in delayed onset increased blood pressure and altered vascular remodeling

Abstract

Emerging studies have begun to recognize a role for the immune system in mediating blood pressure, where the depletion or inhibition of immune cells attenuates increased blood pressure in animal models of hypertension. What is less clear, however, is how immunosuppression and the downregulation of specific signaling pathways contributes to the regulation of blood pressure in the absence of a hormonal or other stimulus. The increased incidence of new‐onset hypertension in patients who are prescribed immunosuppressants suggests a relationship between decreased immune activity and hypertension. We investigated this relationship and tested the hypothesis that the suppression of the innate and adaptive immune systems alters vascular structure and blood pressure homeostasis. We induced immunosuppression by treating 11‐week old male C57Bl/6 mice with 4mg of purified anti‐interferon alpha/beta receptor 1 (IFNAR1) antibody via intra‐peritoneal injection. Blood pressure was measured continuously via a radiotelemetry transmitter implanted in the left carotid artery for up to 11 weeks post anti‐IFNAR1 treatment. Following blood pressure recordings, animals were sacrificed and blood vessels including the aorta, renal artery and mesenteric vessel pairs were isolated and analyzed by histology for changes in vascular protein expression and vessel remodeling. Beginning ~10 days post anti‐IFNAR1 treatment, immunosuppressed mice developed increased mean arterial pressure (MAP) during their active period (night), that was attributable to both increased diastolic and systolic blood pressures. Comparatively, only diastolic pressures increased during the rest period (day), resulting in a MAP that was not significantly increased. These changes in pressure were sustained up to 25 days post anti‐IFNAR1 treatment. At 6, 8 and 11 weeks post anti‐IFNAR1, daytime blood pressures in immunosuppressed animals were comparable to control mice while nighttime systolic, diastolic and MAPs remained elevated. Histological analysis of vessels collected 11 weeks after anti‐IFNAR1 treatment showed altered lumen diameter and medial thickness in the aorta and renal arteries. Our findings show a role for immunosuppression in regulating blood pressure homeostasis and vascular structure, and begin to identify mechanisms of remodeling that may be involved. Future work will how investigate key vascular signaling pathways and how they are altered during immunosuppression and the resulting hypertension.Support or Funding InformationFord Foundation Postdoctoral Grant (IAMB), HL 088554 R01 (BEI)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.