Renal Denervation and Celiac Ganglionectomy Decrease Mean Arterial Pressure Similarly in Genetically Hypertensive Schlager (BPH/2J) Mice

Author:

Asirvatham-Jeyaraj Ninitha12,Gauthier Madeline M.3,Banek Christopher T.13ORCID,Ramesh Abhismitha1ORCID,Garver Hannah4,Fink Gregory D.4ORCID,Osborn John W.1

Affiliation:

1. From the Department of Integrative Biology and Physiology, University of Minnesota, Minneapolis (M.M.G., C.T.B., A.R., J.W.O.)

2. Department of Biotechnology, Indian Institute of Technology Madras, Chennai (N.A.-J.)

3. Department of Physiology, University of Arizona, Tucson (M.M.G., C.T.B.)

4. Department of Pharmacology and Toxicology, Michigan State University, East Lansing (H.G., G.D.F.).

Abstract

Renal denervation (RDNX) lowers mean arterial pressure (MAP) in patients with resistant hypertension. Less well studied is the effect of celiac ganglionectomy (CGX), a procedure which involves the removal of the nerves innervating the splanchnic vascular bed. We hypothesized that RDNX and CGX would both lower MAP in genetically hypertensive Schlager (BPH/2J) mice through a reduction in sympathetic tone. Telemeters were implanted into the femoral artery in mice to monitor MAP before and after RDNX (n=5), CGX (n=6), or SHAM (n=6). MAP, systolic blood pressure, diastolic blood pressure, and heart rate were recorded for 14 days postoperatively. The MAP response to hexamethonium (10 mg/kg, IP) was measured on control day 3 and postoperative day 10 as a measure of global neurogenic pressor activity. The efficacy of denervation was assessed by measurement of tissue norepinephrine. Control MAP was similar among the 3 groups before surgical treatments (≈130 mm Hg). On postoperative day 14, MAP was significantly lower in RDNX (−11±2 mm Hg) and CGX (−11±1 mm Hg) groups compared with their predenervation values. This was not the case in SHAM mice (−5±3 mm Hg). The depressor response to hexamethonium in the RDNX group was significantly smaller on postoperative day 10 (−10±5 mm Hg) compared with baseline control (−25±10 mm Hg). This was not the case in mice in the SHAM (day 10; −28±5 mm Hg) or CGX (day 10; −34±7 mm Hg) group. In conclusion, both renal and splanchnic nerves contribute to hypertension in BPH/2J mice, but likely through different mechanisms.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Internal Medicine

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