Targeted afferent renal denervation reduces arterial pressure but not renal inflammation in established DOCA-salt hypertension in the rat.

Abstract

Recent preclinical studies show renal denervation (RDNx) may be an effective treatment for hypertension; however, the mechanism remains unknown. We have recently reported total RDNx (TRDNx) and afferent-selective RDNx (ARDNx) similarly attenuated the development of deoxycorticosterone acetate (DOCA)-salt hypertension. Whereas TRDNx abolished renal inflammation, ARDNx had a minimal effect despite an identical antihypertensive effect. Although this study established that ARDNx attenuates the development of DOCA-salt hypertension, it is unknown whether this mechanism remains operative once hypertension is established. The current study tested the hypothesis that TRDNx and ARDNx would similarly decrease mean arterial pressure (MAP) in the DOCA-salt hypertensive rat, and only TRDNx would mitigate renal inflammation. After 21 days of DOCA-salt treatment, male Sprague-Dawley rats underwent TRDNx ( n = 16), ARDNx ( n = 16), or Sham ( n = 14) treatment and were monitored for 14 days. Compared with baseline, TRDNx and ARDNx decreased MAP similarly (TRDNx -14 ± 4 and ARDNx -15 ± 6 mmHg). After analysis of diurnal rhythm, rhythm-adjusted mean and amplitude of night/day cycle were also reduced in TRDNx and ARDNx groups compared with Sham. Notably, no change in renal inflammation, injury, or function was detected with either treatment. We conclude from these findings that: 1) RDNx mitigates established DOCA-salt hypertension; 2) the MAP responses to RDNx are primarily mediated by ablation of afferent renal nerves; and 3) renal nerves do not contribute to the maintenance of renal inflammation in DOCA-salt hypertension.

• Authors: Christopher T Banek, Madeline M Gauthier, Daniel C Baumann, Dusty Van Helden, Ninitha Asirvatham-Jeyaraj, Angela Panoskaltsis-Mortari, Gregory D Fink, John W Osborn
• Journal: American journal of physiology. Regulatory, integrative and comparative physiology (Am J Physiol Regul Integr Comp Physiol) Vol. 314 Issue 6 Pg. R883-R891 (06 01 2018) ISSN: 1522-1490 [Electronic] United States
• PMID: 29513561 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Desoxycorticosterone Acetate

Topics

• Animals
• Arterial Pressure
• Circadian Rhythm
• Denervation
• Desoxycorticosterone Acetate
• Hypertension (chemically induced, physiopathology)
• Kidney (innervation)
• Male
• Nephritis (chemically induced, physiopathology)
• Neurons, Afferent
• Rats
• Rats, Sprague-Dawley
• Sympathetic Nervous System (physiopathology)