Mechanisms of baroreceptor activation.
The determinants of the nerve activity generated at the baroreceptor endings have been examined. 1) In the isolated carotid sinus, the placement of activated bovine aortic endothelial cells decreased baroreceptor activity (BRA) in a reversible manner. Both endothelin and nitric oxide (NO) suppress BRA, whereas prostacyclin (PGI2) increases activity. 2) The BRA in single units declines and often ceases during non-pulsatile increases in carotid sinus pressure sustained over several minutes. This "adaptation" is attenuated by the transient potassium channel (IA) blocker 4-aminopyridine (4-AP) and not by inhibition of the Na+/K+ pump. 3) In preliminary studies, mechano-electrical transduction was examined in isolated and cultured nodose ganglion neurons. Opening of stretch-activated (SA) channels by suction on the cell-attached patch was seen infrequently; however, probing the neurons consistently increased their intracellular calcium [Ca++]i measured with fura-2. This increase in [Ca++]i is blocked by gadolinium (Gd3+), a trivalent lanthanide reported to block SA channels. Gd3+ also blocks the BRA in the carotid sinus. We conclude that paracrine factors significantly modulate BR sensitivity, that selective ionic mechanisms (the 4-AP sensitive K+ channels) determine the degree of "adaptation" of BR to elevated pressure, and that SA channels sensitive to Gd3+ may be the mechano-electrical transducers in BR neurons.
Chapleau
M W
MW
Department of Internal Medicine, University of Iowa, Iowa City, U.S.A.
Hajduczok
G
G
Sharma
R V
RV
Wachtel
R E
RE
Cunningham
J T
JT
Sullivan
M J
MJ
Abboud
F M
FM
D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D002346:Carotid Sinus / Q000502:physiology; D004285:Dogs; D004730:Endothelium, Vascular / Q000502:physiology; D006973:Hypertension / Q000503:physiopathology; D066298:In Vitro Techniques; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000378:metabolism; D011311:Pressoreceptors / Q000187:drug effects / Q000502:physiology*; D011817:Rabbits; D051381:Rats; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
D026902:Potassium Channel Blockers; D015221:Potassium Channels; D015761:4-Aminopyridine; D000254:Sodium-Potassium-Exchanging ATPase