title: Sympatholytic effect of clonidine depends on the respiratory phase in rat splanchnic nerve.
abstract: Peri-event averaging of the sympathetic nerve discharge was done to measure the magnitude of the sympatholytic effect of the anti-hypertensive drug clonidine during three different phases of the respiratory cycle (inspiration, I; postinspiration, post-I; late expiration, pre-I). Arterial pressure (AP) and discharges of splanchnic sympathetic (SND) and phrenic nerves (PND, onset used for peri-event averaging) were recorded in urethane-anesthetized, vagotomized, aortic deafferentated, paralyzed and artificially ventilated Sprague-Dawley rats (n = 7). During control periods (mean AP 106 +/- 10 mmHg) SND was distributed equally throughout the three selected respiratory periods, though two brief peaks were noted during the I and post-I periods. Low doses of clonidine (15-30 micrograms/kg i.v.) produced brief hypertension (< 30 s, 150 +/- 9 mmHg at peak) followed by moderate hypotension (89 +/- 3 mmHg) and a reduction in mean SND (-63 +/- 11% from control value). High doses of clonidine (200-250 micrograms/kg i.v.) produced sustained hypertension (> 10 min, 173 +/- 3 mmHg) and silence of SND. During this sustained hypertension, lowering AP by i.v. nitroprusside retrieved a component of SND that was barosensitive but insensitive to clonidine. During those hypotensive periods (spontaneous after a low dose of clonidine, and induced by nitroprusside after a high dose of clonidine), SND was most attenuated during the pre-I period and least during the I period. The I component of SND was significantly less attenuated than the post-I component by clonidine and, in most cases (6 out of 7), SND showed a single inspiratory peak following clonidine administration. It is concluded that (i) the pre-I component of SND is the most sensitive to clonidine and (ii) the I component of SND is the most resistant to the drug.
authors.affiliation: Department of Pharmacology, University of Virginia Health Sciences Center, Charlottesville 22908, USA.
authors.forename: N
authors.initials: N
authors.lastname: Koshiya
authors.forename: P G
authors.initials: PG
authors.lastname: Guyenet
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D002245:Carbon Dioxide / Q000378:metabolism; D003000:Clonidine / Q000494:pharmacology*; D008297:Male; D009599:Nitroprusside / Q000494:pharmacology; D010791:Phrenic Nerve / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015656:Respiratory Mechanics / Q000502:physiology*; D013153:Splanchnic Nerves / Q000187:drug effects / Q000502:physiology*; D013565:Sympatholytics / Q000494:pharmacology*
chemical_list: D013565:Sympatholytics; D002245:Carbon Dioxide; D009599:Nitroprusside; D003000:Clonidine