Prenatal nicotine exposure impairs beta-adrenergic function: persistent chronotropic subsensitivity despite recovery from deficits in receptor binding.
Gestational exposure to nicotine has been shown to interfere with biochemical markers of development of central and peripheral noradrenergic activity. The current study examines the development and function of cardiac beta-adrenergic receptors in the offspring of pregnant rats given nicotine infusions of 6 mg/kg/day from gestational days 4 through 20, administered by subcutaneously implanted osmotic minipumps. Prenatal nicotine exposure delayed the development of beta-adrenergic receptor binding capabilities, as assessed with [125I]pindolol in membrane preparations from heart and kidney. The deficits in receptor binding were associated with marked subsensitivity of chronotropic responses to administration of a beta-adrenergic agonist, isoproterenol. Although the effects on receptor binding resolved after weaning, functional deficiencies in responsiveness to isoproterenol or to preganglionic electrical stimulation of sympathetic nerves to the heart persisted into adulthood. These results indicate that prenatal exposure to nicotine produces long-term alterations in adrenergic responsiveness of sympathetic target tissues.
Navarro
H A
HA
Department of Pharmacology, Duke University Medical Center, Durham, NC 27710.
Mills
E
E
Seidler
F J
FJ
Baker
F E
FE
Lappi
S E
SE
Tayyeb
M I
MI
Spencer
J R
JR
Slotkin
T A
TA
D000375:Aging; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D005260:Female; D006321:Heart / Q000187:drug effects / Q000254:growth & development* / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects*; D007545:Isoproterenol / Q000494:pharmacology; D008431:Maternal-Fetal Exchange; D009538:Nicotine / Q000494:pharmacology*; D009929:Organ Size / Q000187:drug effects; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology*; D012016:Reference Values
D011943:Receptors, Adrenergic, beta; D009538:Nicotine; D007545:Isoproterenol