Ablation of renin from the nucleus ambiguus in male mice elevated baseline heart rate compared to controls (546 vs 514 bpm; p<0.01) due to increased cardiac sympathetic nerve activity.
Does conditional ablation of renin from the nucleus ambiguus alter heart rate and autonomic balance in male mice?
Renin in the nucleus ambiguus plays a role in maintaining autonomic balance by suppressing cardiac sympathetic tone under physiological conditions, but not during DOCA-salt hypertension.
Absolute Event Rate: 546% vs 514%
p-value: p=<0.01
The brain renin-angiotensin system (RAS) contributes to the development of hypertension via modulation of the autonomic nervous system. While it is accepted that the brain RAS elevates sympathetic nerve activity (SNA), its contribution to parasympathetic nervous system (PNS) activity remains understudied. Unexpectedly, we identified renin-expressing cardiovagal neurons in the nucleus ambiguus (NuAm), a region known for regulating cardiac PNS function. Therefore, we hypothesized that renin in the NuAm plays an important role in PNS control. This hypothesis was tested in male mice under physiological conditions or under deoxycorticosterone acetate (DOCA)-salt hypertension, a model previously associated with elevated brain RAS activity.To test this hypothesis, we conditionally ablated renin from the NuAm (RenNuAm-KO). Briefly, mice carrying the floxed allele of exon1a of the renin locus (Renflox) were subjected to NuAm-targeted stereotactic microinjections of adeno-associated viruses (AAV)-carrying either Cre-recombinase (AAV-Cre, N=10) or control virus (AAV-Empty, N=7). Heart rate (HR) and blood pressure (BP) were recorded via radiotelemetry. Subsequently, responses to propranolol (5 mg/kg, IP) or methylatropine (2 mg/kg, IP) were compared against saline injections. The same studies were conducted in the same mice under DOCA-salt HT. At baseline, RenNuAm-KO had higher HR during the light cycle compared to WT (546 ± 5 bpm vs 514 ± 9 bpm; p< 0.01). To dissect the influence of renin in the NuAm on cardiac SNA and PNA, we conducted pharmacological blockade studies. RenNuAm-KO exhibited greater reduction in HR in response to cardiac SNA blockade with propranolol (ΔHR: 95 ± 12 vs 5 ± 17 bpm; p =0.05), suggesting elevated cardiac sympathetic tone in the absence of renin in the NuAm. RenNuAm-KO showed a non-statistically significant trend toward a smaller HR increase in response to cardiac PNA blockade with methylatropine compared to WT (ΔHR: 37 ± 22 vs 85 ± 32 bpm; p=0.22), suggesting that cardiac vagal tone appears to be preserved. After week 3 with DOCA-salt, no differences in HR between groups were observed. However, increased cardiac sympathetic activity observed at baseline appears attenuated in the RenNuAm-KO, evidenced by a similar bradycardic response after propranolol (ΔHR: 48±15 vs 67 ± 31 bpm). Additionally, both groups have similar HR responses to methylatropine (ΔHR: 26.0 ± 21 vs 71±20 bpm). Thus, these data suggest that under DOCA-salt, renin in the NuAm does not alter cardiac autonomic nerve activity. This study indicates that renin in the NuAm maintains autonomic balance in healthy conditions in male mice. When renin is absent in the NuAm, baseline HR is elevated due to increased cardiac SNA. Yet, during DOCA-salt hypertension, renin in the NuAm does not seem to be required for maintaining autonomic balance. Ongoing studies will explore the role of renin in the NuAm under varying conditions, such as exposure to different temperatures, and determine the contribution of sex as a biological variable. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.
Kaminski et al. (Fri,) conducted a other in Normotensive and DOCA-salt hypertension (n=17). NuAm-targeted stereotactic microinjections of AAV-Cre (RenNuAm-KO) vs. AAV-Empty (WT) was evaluated on Baseline heart rate during the light cycle (p=<0.01). Ablation of renin from the nucleus ambiguus in male mice elevated baseline heart rate compared to controls (546 vs 514 bpm; p<0.01) due to increased cardiac sympathetic nerve activity.