Figure 3. GLP1 receptors modulate basal and chemoreflex-evoked sympathetic nerve activity mediated by the peripheral chemoreceptors.

(a) Diagram of in situ working heart-brainstem preparation (WHBP). Recordings were made unilaterally targeting the right CB while contralateral common carotid artery was occluded. NaCN was administered into the thoracic aorta to evoke peripheral chemoreflex response. ECG - electrocardiogram, tSNA - thoracic sympathetic activity, PNA - phrenic nerve activity, PP - pulse pressure.

(b) Drugs were precisely administered to the CB via cannulated internal carotid artery (ICA). After accessing the CB, drugs were washed off via the external carotid artery (ECA) bypassing the brain. CSN − carotid sinus nerve.

(c) Changes in basal tSNA in response to Exendin-4 and (d) Exendin-3 administration in Wistar and SH rats. n=4.

(e) Experimental protocol for testing the peripheral CB chemoreceptor sensitivity over a series of chemoreflex challenges.

(f) Changes in CSN activity in response to Exendin-4 administration in Wistar rats. n=6. Kruskal-Wallis test, Dunn’s post-hoc test (Bonferroni correction).

(g) Raw and integrated chemoreflex-evoked CSN activity traces before and 2 min following Ex-4 administration. Representative traces selected based on similarity to average values obtained across all animals for control and 2 min timepoints.

(h) Representative traces of chemoreflex-evoked HR and integrated tSNA responses to NaCN at baseline and 20minutes following Exendin-4 administration in Wistar and SH rats. Representative traces selected to best match the average values obtained across all animals.

(i) Changes in chemoreflex-evoked tSNA response following Exendin-4 (n=8) and (j) Exendin-3 (n=6) administration in Wistar and SH rats.

Non-parametric Friedman test (within-group) and the Kruskal-Wallis test (between-group), Dunn’s post-hoc test (Bonferroni correction). Arrows indicate NaCN bolus. Mean ± SEM.