Bardet Biedl syndrome genes are required for autonomic control of the circulation

Abstract

Bardet Biedl syndrome (BBS) is a pleiotropic autosomal recessive disorder with several features including hypertension and cardiovascular disease. The 16 Bbs genes identified so far have been implicated in the regulation of several physiological functions. Here, we used the knock‐in Bbs1M390R mouse model that phenocopy human BBS to test the hypothesis that Bbs genes are important for autonomic function. Baroreflex sensitivity (BRS) was examined in conscious state using the responses of renal sympathetic activity, arterial pressure and heart rate (HR) to the sequential intravenous injection of sodium nitroprusside and phenylephrine (PE). Notably, the maximum gain of the baroreflex was reduced in the Bbs1M390R mice (0.8±0.5%) vs. controls (3.3±0.9%, P<0.01). Direct recording of baroreceptor activity from the aortic depressor nerve (ADN) during PE‐induced hypertension which provides another measure of BRS revealed attenuated ADN baroreflex response in Bbs1M390R mice (6±2%) vs. controls (12±3%, P<0.05). Finally, analysis of the central component of the baroreflex with electrical stimulation (40 Hz) of the ADN showed an attenuated HR reflex response in Bbs1M390R mice (−47±16 bpm) vs. controls (−88±15 bpm, P<0.03) indicating that the impairment in BRS in BBS mice is centrally‐mediated. Our data demonstrates that Bbs genes are critically involved in the autonomic regulation of the cardiovascular function.