Long-term systemic hemodynamic effects of cotinine in rats.
Cigarette smoking has been epidemiologically correlated with lower BP in humans, despite the acute BP effects of nicotine. Cotinine, a primary metabolite of nicotine, has been suggested as a mediator of the BP-lowering effect of smoking. To determine the cardiovascular effects of cotinine itself, arterial BP was monitored continuously in chronically instrumented Sprague-Dawley rats before, during, and after 14 days of intraarterial (i.a.) infusion of cotinine or placebo. Cardiovascular data were collected and analyzed by microcomputer for diurnal changes and for light- and dark-cycle averages. Heart rate (HR) was higher in both precotinine and placebo groups during the dark cycle than during the light cycle. HR was significantly lower (p < 0.025) during cotinine infusion in the cotinine group as compared with placebo. Five days after cotinine infusion, however, HR was not different from that of placebo controls. Arterial BP was not different between cotinine- and placebo-treated rats at any time period. The difference between HR but not arterial BP suggested that baroreceptor activity might differ after cotinine administration. Baroreceptor activity, assessed by analysis of HR changes evoked by phenylephrine, did not differ before and during cotinine administration, however. We conclude that cotinine did not decrease BP in rats under the present experimental conditions, but that cotinine was probably responsible for the observed bradycardia.
Smith
T L
TL
Department of Physiology and Pharmacology, Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, North Carolina 27157-1083.
Russell
G B
GB
Mosberg
A T
AT
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003367:Cotinine / Q000008:administration & dosage / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D007262:Infusions, Intravenous; D008297:Male; D011311:Pressoreceptors / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
D003367:Cotinine