The Effect of Angiotensin Receptor Blockade Using Losartan in Otoprotection Against Noise-Induced Hearing Loss

Sunday, September 29, 2024

10:06 AM – 10:12 AM EDT

Location: MBCC, 231

Disclosure(s):

Carolina Chu, MS:

faculty for this accredited education activity has no relationship(s) with ineligible companies to disclose.

Miles J. Klimara, MD:

faculty for this accredited education activity has no relationship(s) with ineligible companies to disclose.

Douglas M. Bennion, MD, PhD:

faculty for this accredited education activity has no relationship(s) with ineligible companies to disclose.

Introduction: Noise trauma impairs cochlear microcirculation through a variety of mechanisms resulting in hearing loss. Losartan, an angiotensin II receptor antagonist, is anti-inflammatory and vasoprotective in acute and chronic diseases of the heart, kidneys, and brain, and is a promising candidate treatment in attenuating noise-induced hearing loss.

Methods: CBA/J mice (age 9-10 weeks, n = 4-7 per group) were randomized to standard or losartan-infused chow (20 mg/kg/day, ~100 mg daily dose in humans) starting three days prior to exposure to two hours of 8-16k octave band noise at 102.5 dB SPL (males)/105 dB SPL (females) for temporary threshold shifts or 105 dB SPL (males)/107.5 dB SPL (females) for permanent threshold shifts. Auditory brainstem responses (ABR) were recorded up to two weeks after noise exposure. Cochleae were whole-mounted and immunostained for inner hair cell (IHC) synapse counting. Studies were conducted from July 2023-Jenuary 2024.

Results: One day after moderate-intensity noise exposure, losartan treatment blunted temporary ABR threshold shifts (p < 0.02) at 16kHz (16 vs 5 dB SPL shift in control and losartan-treated animals respectively) and 32kHz (18 vs 1 dB SPL shift). ABR thresholds returned to baseline by 14 days post-exposure. However, the control group had fewer mean synapses per IHC relative to the losartan-treated group (15.3 vs 19.9 synapses/IHC, p < 0.02). In a second cohort, one day after high-intensity noise exposure, losartan again blunted ABR threshold increases (p < 0.02), a protective effect that persisted to 14 days with significantly (p < 0.05) lower permanent threshold shifts with losartan treatment at 8kHz (15 vs 2 dB SPL shift), 16kHz (33 vs 5 dB SPL shift), 32kHz (19 vs 0 dB SPL shift), and click stimulus (18 vs 4 dB SPL shift). Additionally, losartan resulted in significantly improved ABR wave 1 latencies and amplitude growth function compared to control at 14 days (p < 0.05).

Conclusions: Losartan provides an otoprotective effect against both temporary and permanent ABR threshold shifts after noise overexposure and exhibits protection against noise-induced cochlear synaptopathy.

Presenting Author(s)

Carolina Chu, MS

Medical Student
University of Iowa, Carver College of Medicine
Coralville, Iowa, United States

Disclosure(s):
faculty for this accredited education activity has no relationship(s) with ineligible companies to disclose.

Co-Author(s)

TK

Tanner J. Kempton, MD

Resident
University of Iowa, Department of Otolaryngology
Iowa City, IA, United States

Disclosure information not submitted.
Peter Eckard, BS

Medical Student
Department of Otolaryngology-Head and Neck Surgery, University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States

Disclosure information not submitted.
RH

Rong Zhuo Hua, BS

Student
University of Iowa, United States

Disclosure information not submitted.
BH

Bryce Hunger, BS

Student
University of Iowa, United States

Disclosure information not submitted.
MK

Miles J. Klimara, MD

Resident Physician
University of Iowa Hospitals & Clinics
Iowa City, IA, United States

Disclosure(s):
faculty for this accredited education activity has no relationship(s) with ineligible companies to disclose.

Senior Author(s)

MH

Marlan R. Hansen, MD

Professor and Chair
Univ of Iowa
Iowa City, IA, United States

Disclosure information not submitted.
Douglas M. Bennion, MD, PhD

Neurotology Fellow
University of California San Diego
Iowa City, IA, United States

Disclosure(s):
faculty for this accredited education activity has no relationship(s) with ineligible companies to disclose.