Characteristics of renal sympathetic nerve single units in rabbits with angiotensin-induced hypertension

Sandra L. Burke, Elena V. Lukoshkova, Geoffrey A. Head

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Abstract

New Findings: What is the central question of this study? Is the elevated whole renal nerve activity observed with chronic low-dose angiotensin the result of recruitment or changes in firing frequency of renal neurons? What is the main finding and its importance? Resting firing frequency of renal neurons is lower with low-dose angiotensin, but cardiac rhythmicity is reduced by high-dose angiotensin. Unitary responses to baroreceptor stimulation are reduced, but there is greater sensitivity of central chemoreceptor pathways. Elevated nerve activity in conscious animals is the result of recruitment of individual neurons normally silent but available for recruitment during physiological challenge. We examined the effect of chronic angiotensin (Ang II)-induced hypertension on activity of postganglionic renal sympathetic units to determine whether altered whole renal nerve activity is due to recruitment or changes in firing frequency. Rabbits were treated with a low (20 ng kg−1 min−1, 8 weeks) or high dose (50 ng kg−1 min−1, 4 weeks) of Ang II before the experiment under chloralose–urethane anaesthesia. Spontaneously active units were detected from multiunit recordings using an algorithm that separated units by action potential shape using templates that matched spikes within a prescribed standard deviation. Multiunit sympathetic nerve activity was 40% higher in rabbits treated with low-dose Ang II than in sham (P = 0.012) but not different in high-dose Ang II. Resting firing frequency was similar in sham rabbits (1.00 ± 0.09 spikes s−1, n = 144) and in those treated with high-dose Ang II (1.10 ± 0.08 spikes s−1, n = 112) but was lower with low-dose Ang II (0.65 ± 0.08 spikes s−1, n = 149, P < 0.05). Unit firing rhythmicity was linked to the cardiac cycle and was similar in sham and low-dose Ang II groups but 29–32% lower in rabbits treated with high-dose Ang II (P < 0.001). Cardiac linkage followed a similar pattern during hypoxia. All units showed baroreceptor dependency. Baroreflex gain and range were reduced and curves shifted to the right in Ang II groups. Firing frequency during hypoxia increased by +39% in low-dose Ang II and +82% in shams, but the greatest increase was in the high-dose Ang II group (+103%, Pdose = 0.001). Responses to hypercapnia were similar in all groups. Increases in sympathetic outflow in hypertension caused by low-dose chronic Ang II administration are due to recruitment of neurons, but high-dose Ang II increases firing frequency in response to chemoreceptor stimuli independently of the arterial baroreceptors.

Original languageEnglish
Pages (from-to)50-66
Number of pages17
JournalExperimental Physiology
Volume101
Issue number1
DOIs
Publication statusPublished - 1 Jan 2016

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