Revealing the role of the autonomic nervous system in the development and maintenance of Goldblatt hypertension in rats

Abstract

Despite extensive use of the renovascular/Goldblatt model of hypertension—2K-1C, and the use of renal denervation to treat drug resistant hypertensive patients, autonomic mechanisms that underpin the maintenance of this hypertension are important yet remain unclear. Our aim was to analyse cardiovascular autonomic function by power spectral density analysis of both arterial pressure and pulse interval measured continuously by radio telemetry for 6 weeks after renal artery clipping. Mean arterial pressure increased from 106 ± 5 to 185 ± 2 mm Hg during 5 weeks post clipping when it stabilized. A tachycardia developed during the 4th week, which plateaued between weeks 5 and 6. The gain of the cardiac vagal baroreflex decreased immediately after clipping and continued to do so until the 5th week when it plateaued (from − 2.4 ± 0.09 to − 0.8 ± 0.04 bpm/mm Hg; P < 0.05). A similar time course of changes in the high frequency power spectral density of the pulse interval was observed (decrease from 13.4 ± 0.6 to 8.3 ± 0.01 ms2; P < 0.05). There was an increase in both the very low frequency and low frequency components of systolic blood pressure that occurred 3 and 4 weeks after clipping, respectively. Thus, we show for the first time the temporal profile of autonomic mechanisms underpinning the initiation, development and maintenance of renovascular hypertension including: an immediate depression of cardiac baroreflex gain followed by a delayed cardiac sympathetic predominance; elevated sympathetic vasomotor drive occurring after the initiation of the hypertension but coinciding during its mid-development and maintenance.