Ozone Exposure Induces Beta‐Adrenergic Insensitivity

The association between ambient ozone (O 3 ) and adverse cardiopulmonary outcomes has long been recognized. Acute O 3 classically induces bradycardia, hypotension, and increases heart rate variability – all of which are affected by the heart's response to sympathetic output. To test whether O 3 exposure changes the sensitivity of the heart to beta adrenergic stimulus, C57BL/6 mice (n=10) were exposed to either Room Air (RA) 24 hours of 0.3 ppm O 3 and then underwent in‐vivo hemodynamic assessment and isoproterenol (Iso) challenge involving I.V. bolus doses at half log intervals. Mice exposed to O 3 displayed decreased left ventricular systolic function as characterized by decreased heart rate 565 bpm vs. 595 bmp in RA; systolic pressure decreased from 106 mmHg in RA mice to 87 mmHg in O 3 exposed mice; dP/dT max decreased 10% with O 3 exposure. Diastolic function was also depressed by O 3 exposure: dP/dT min increased by 25% and Tau (Log) increased by 30% with O 3 exposure. O 3 exposure resulted in a decreased response to Iso as indicated by a leftward shift in the dose‐response curve. At the maximal dose (6 ng Iso in 10 μL PBS) heart rate increased by 60 bpm in RA controls and 35 bpm in O 3 treated mice; dP/dT max increased by 6000 mmHg/s in control and only increased by 3000 mmHg/s in O 3 exposed mice. In addition to confirming the systolic and diastolic dysfunction typically associated with O 3 , this study demonstrates that acute O 3 exposure induces beta adrenergic insensitivity – a condition thought to contribute to heart failure in patients with heart disease that may be important in understanding the deleterious cardiopulmonary effects of inhaled O 3 . NIH R01 HL087033