Portal osmopressor mechanism linked to transient receptor potential vanilloid 4 and blood pressure control.
Human subjects with impaired baroreflex function cannot buffer rises or falls in blood pressure (BP), thus allowing BP effects of endogenous or environmental stimuli that previously escaped detection to emerge dramatically. Studies in these patients led us to discover that water ingestion induced a robust increase in BP and vascular resistance. Here, using a mouse model of baroreflex impairment, we show that the increase in blood pressure after water ingestion is mediated through sympathetic nervous system activation and that the osmosensitive transient receptor potential vanilloid 4 channel (Trpv4) is an essential component of the response. Although portal osmolality decreases after water ingestion in both wild-type and Trpv4(-/-) mice, only the wild-type animals show a pressor response. The same volume of physiological saline does not elicit an increase in BP, suggesting osmolality as the stimulus. The osmopressor response to water, and Trpv4 thus represent new factors now implicated in the physiology of BP regulation.
McHugh
Julia
J
Autonomic Dysfunction Center, Departments of Medicine, Vanderbilt University, Nashville, TN 37232-2195, USA.
Keller
Nancy R
NR
Appalsamy
Martin
M
Thomas
Steven A
SA
Raj
Satish R
SR
Diedrich
André
A
Biaggioni
Italo
I
Jordan
Jens
J
Robertson
David
D
D000818:Animals; D017704:Baroreflex / Q000187:drug effects* / Q000502:physiology; D001795:Blood Pressure Determination; D004195:Disease Models, Animal; D006801:Humans; D006973:Hypertension / Q000378:metabolism / Q000503:physiopathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009997:Osmotic Pressure; D011224:Prazosin / Q000494:pharmacology; D011336:Probability; D011897:Random Allocation; D018709:Statistics, Nonparametric; D013564:Sympathetic Nervous System / Q000502:physiology*; D050916:TRPV Cation Channels / Q000502:physiology*; D014628:Vagotomy / Q000379:methods; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology; D014867:Water / Q000008:administration & dosage*; D014882:Water-Electrolyte Balance / Q000502:physiology
D050916:TRPV Cation Channels; D014867:Water; D011224:Prazosin
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