Liver afferents contribute to water drinking-induced sympathetic activation in human subjects: a clinical trial.
Water drinking acutely increases sympathetic activity in human subjects. In animals, the response appears to be mediated through transient receptor potential channel TRPV4 activation on osmosensitive hepatic spinal afferents, described as osmopressor response. We hypothesized that hepatic denervation attenuates water drinking-induced sympathetic activation. We studied 20 liver transplant recipients (44±2.6 years, 1.2±0.1 years post transplant) as model of hepatic denervation and 20 kidney transplant recipients (43±2.6 years, 0.8±0.1 years post transplant) as immunosuppressive drug matched control group. Before and after 500 ml water ingestion, we obtained venous blood samples for catecholamine analysis. We also monitored brachial and finger blood pressure, ECG, and thoracic bioimpedance. Plasma norepinephrine concentration had changed by 0.01±0.07 nmol/l in liver and by 0.21±0.07 nmol/l in kidney transplant recipients (p<0.05 between groups) after 30-40 minutes of water drinking. While blood pressure and systemic vascular resistance increased in both groups, the responses tended to be attenuated in liver transplant recipients. Our findings support the idea that osmosensitive hepatic afferents are involved in water drinking-induced sympathetic activation in human subjects.


BACKGROUND
ClinicalTrials.gov NCT01237431.
Institute of Clinical Pharmacology, Medical School Hannover, Hannover, Germany.
Marcus
M
May
Faikah
F
Gueler
Hannelore
H
Barg-Hock
Karl-Heinz
KH
Heiringhoff
Stefan
S
Engeli
Karsten
K
Heusser
André
A
Diedrich
André
A
Brandt
Christian P
CP
Strassburg
Jens
J
Tank
Fred C G J
FC
Sweep
Jens
J
Jordan
D000293:Adolescent; D000328:Adult; D000344:Afferent Pathways / Q000502:physiology / Q000601:surgery; D002395:Catecholamines / Q000097:blood; D003714:Denervation; D004326:Drinking / Q000502:physiology*; D060766:Drinking Water / Q000008:administration & dosage*; D005260:Female; D006439:Hemodynamics; D006801:Humans; D008099:Liver / Q000294:innervation* / Q000601:surgery; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D013564:Sympathetic Nervous System / Q000502:physiology* / Q000601:surgery; D013997:Time Factors; D055815:Young Adult
D002395:Catecholamines; D060766:Drinking Water