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Abstract: PO2151

The Effect of Epidermal Growth Factor Inhibition on Diurnal Variation of Blood Pressure in Mice

Session Information

Category: Hypertension and CVD

  • 1403 Hypertension and CVD: Mechanisms

Authors

  • King, Keyona, Emory University School of Medicine, Atlanta, Georgia, United States
  • Hoover, Robert S., Emory University School of Medicine, Atlanta, Georgia, United States
Background

There are 78 million adults in the United States who have hypertension (HTN). HTN is a serious medical condition that serves as risk factor for cardiovascular disease (CVD) and chronic kidney disease (CKD). Blood pressure (BP) normally declines about 10% during sleep and this is called “dipping”. Studies have demonstrated that an attenuated decline in nocturnal BP (“non-dipping”) is associated with increased cardiovascular risks. Investigations by our group and others have demonstrated an effect of the epidermal growth factor (EGF) on sodium transport proteins and BP. However, an association between EGF and “dipping” has not been described.

Methods

Using radio-telemetry in five male mice ages 7 weeks old, we collected the systolic blood pressure (SBP) measurements over 24 hours daily for two weeks. These animals received a low salt (LS) diet (0.4% Na chow) for 6 days and high salt (HS) diet (4% Na chow) for 8 days. Only the experimental (E) group (n=3) received gefitinib (an EGF receptor inhibitor) at a regimen of 100 mg/kg/d given orally while the control (C) group (n=2) received a placebo. The change in SBP was evaluated during rest (9am-9pm) which are morning hours versus awake (9pm-9am) during evening hours since mice are nocturnal.

Results

The results showed the E group had less of a decrease in their SBP during sleep than the C group (E group: -9.7 ± 0.016 vs. C group: -14.4 ± 0.34 mmHg, p<0.001; delta = 4.7 mmHg, p<0.001). When increasing the dietary Na+ intake by giving the HS diet, once again the E group demonstrated an attenuation of their ability to lower their SBP during resting compared to the C group (E group: -7.3 ± 0.18 vs. C group: -13.5 ± 0.38 mmHg, p<0.001). Here the delta is 6.1 mmHg, p<0.001, which shows that the C group maintained a greater decrease in their resting SBP compared to the E group.

Conclusion

Overall, our results suggest that inhibition of EGF leads to decreased dipping in SBP regardless of the dietary Na intake and this effect is greater with a high dietary Na intake. Therefore, our data is the first to suggest that EGF may play a role in the nocturnal dipping of BP, which could have potential implications for managing HTN-related cardiovascular disease.

Funding

  • NIDDK Support