Mechanism of baroreceptor adaptation in dogs: attenuation of adaptation by the K+ channel blocker 4-aminopyridine.
1. Increased arterial pressure increases baroreceptor activity but activity declines (i.e. baroreceptors adapt) as the pressure is maintained at the higher level. The purpose of this study was to investigate the role of a 4-aminopyridine (4-AP)-sensitive K+ current in causing baroreceptor adaptation. 2. Multi- and single fibre recordings of baroreceptor activity were obtained from the vascularly isolated carotid sinus in anaesthetized dogs during step increases in carotid sinus pressure sustained for periods up to 5 min. 3. Baroreceptor activity increased with the rise in pressure, declined markedly over the first minute, and continued to decline at a slower rate during the remainder of the 5 min period of elevated pressure. Exposure of the isolated carotid sinus to 4-AP (10(-5) and 10(-4) M) attenuated adaptation in a dose-dependent and reversible manner (P < 0.05). 4-AP attenuated the gradual decline in single fibre activity and also prevented derecruitment or dropout of fibres that occurred over time. 4-AP did not alter peak nerve activity measured within the first 2 s of the pressure step. 4. Ouabain (5 x 10(-7)-10(-6) M), an inhibitor of Na+,K(+)-ATPase, increased baroreceptor activity but did not attenuate baroreceptor adaptation. 5. Neither 4-AP nor ouabain altered the distensibility of the carotid sinus as measured with sonomicrometer crystals suggesting that the agents act directly on the nerve endings. 6. The results suggest that activation of a 4-AP-sensitive K+ current contributes significantly to baroreceptor adaptation with little or no contribution of Na+,K(+)-ATPase.
Chapleau
M W
MW
Cardiovascular Center, University of Iowa College of Medicine, Iowa City.
Lu
J
J
Hajduczok
G
G
Abboud
F M
FM
D015761:4-Aminopyridine / Q000494:pharmacology*; D000222:Adaptation, Physiological / Q000187:drug effects*; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D002346:Carotid Sinus / Q000033:anatomy & histology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D010042:Ouabain / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects*; D011311:Pressoreceptors / Q000502:physiology*
D015221:Potassium Channels; D010042:Ouabain; D015761:4-Aminopyridine