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 μg/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 μg/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.