Mechanisms of baroreceptor activation

Abstract

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.

FIG. 1:

Factors from cultured endothelium on microcarrier beads suppress baroreceptor activity of single units. The cultured endothelium was activated with either Ca++ ionophore (A23187, 2 μM) or bradykinin (BK, 10 μM) just before injection of beads into the isolated carotid sinus in dogs. Pth = baroreceptor pressure threshold in mm Hg. Adapted from reference 18 and reproduced with permission of the authors and publisher.

FIG. 2:

Prostacyclin (PGI₂) increases baroreceptor sensitivity (left, n = 11) without altering carotid sinus distensibility (right, n = 5). Reproduced with permission of the authors and publisher (20).

FIG. 3:

Effects of endothelin (ET) on baroreceptor pressure-activity (left) and pressure-diameter (right) relations. The lower concentration of ET (10⁻⁸ M) constricted the carotid sinus but did not influence baroreceptor activity. The higher concentration of ET (10⁻⁷ M) suppressed baroreceptor activity significantly (*P < 0.05) in the absence of any further vasoconstriction, suggesting a direct inhibitory influence on the nerve endings. Adapted from reference 21 and reproduced with permission of the authors and publisher.

FIG. 4:

Adaptation and cessation of activity of a single baroreceptor unit from the isolated carotid sinus of dogs during 5 minutes of elevated static pressure is reversed significantly by 4-AP. Panel A: Continuous recordings of mean baroreceptor activity during step increases in carotid sinus pressure to several levels. Panel B: Shown are the neurograms recorded during the peak increase in activity and after 1 and 5 minutes of elevated pressure (140 mm Hg) for the same fiber as in A. Reproduced with permission of the authors and publisher (27).

FIG. 5:

Stretch-activated (SA) ion channels in dil-labeled nodose ganglion cell. Panel A: Opening of SA channels as indicated by downward deflection of current trace in response to repeated suction on the cell-attached patch. Periods of suction are indicated by horizontal lines above trace. Panel B: Recordings shown with an expanded time scale for 0 and 30 mm Hg suction.

FIG. 6:

The stretch-induced increase in [Ca⁺⁺]_i in nodose neurons is blocked by gadolinium. Mechanical probing of a nodose neuron with a micropipette increased [Ca⁺⁺]_i (upper panel). Probing of the same neuron failed to increase [Ca⁺⁺]_i in the presence of gadolinium (10 μM, lower panel).