A newly published study in Frontiers in Physiology’s Featured Research Topic “Insights in Integrative Physiology: 2021” by CICMD Trainee and Postdoctoral Fellow at the College of Pharmacy, Khalid El Saafien, Ph.D., establishes a novel approach that targets baroreceptors. In the study titled “A Novel Organ-Specific Approach to Selectively Target Sensory Afferents Innervating the Aortic Arch”, El Saafien develops a novel approach that selectively targets mechano-sensory afferents that innervating the aortic arch.
The brain controls and regulates blood pressure at homeostatic levels through circuitry that includes the baroreflex. This circuit comprises of mechano-sensory afferents innervating the aortic arch that employ baroreceptors to convey stretch exerted on the arterial wall to the brain. Although the baroreflex was described more than 80 years ago, the specific molecular, structural, and functional phenotype of the baroreceptors remain uncharacterized. This is due to the lack of tools that provide the genetic and target organ specificity that is required to selectively characterize baroreceptor afferents.
Unlike other circuitry, targeting mechano-sensory afferents innervating the aortic arch is challenging. The aortic arch is located in the thoracic cavity which is difficult to access for recovery surgeries. Furthermore, injection of tracers into the vasculature is problematic. To circumvent these challenges, El Saafien have developed a novel approach that selectively targets and labels mechano-sensory afferents innervating the aortic arch. This approach involves 1) a novel surgical approach that exposes the aortic arch, and 2) the application of viral tracers to the aortic arch by “painting” the virus on the vascular wall.
Using this approach, El Saafien and co-authors were able to validate the specificity and the selectivity of the approach in targeting mechano-sensory afferents innervating the aortic arch. This was done using a number of advanced tools that include, confocal microscopy, RNAscope in situ hybridization, in vitro electrophysiology, in vivo optogenetics, and cardiovascular physiology. “This study, for the first time, provides a sensitive approach to target baroreceptor expressing afferents using genetic manipulation tools that can potentially unravel the specific molecular, structural, and functional phenotype of the baroreceptors,” said El Saafien.
The broad implication of the study is that this approach could be utilized to investigate the contribution of arterial baroreceptors to the etiology or reversal of cardiovascular diseases.