The effects of
anatoxin-A on mean arterial pressure (MAP), heart rate, cardiac index (CI), and blood flow (BF) in hindquarter (HQ), renal (R), and mesenteric (M) vascular beds were studied after intravenous (iv) and intracerebroventricular (icv) administration in the conscious rat. The pharmacological profile of
anatoxin-A was further compared to
nicotine administered iv and icv. MAP and heart rate were measured from femoral artery, CI by thermodilution method, and blood flow by Doppler velocimetry.
Anatoxin-A and
nicotine (30, 100 and 300 micrograms/kg iv) produced an increase in MAP with concomitant
bradycardia. The highest doses increased CI. MBF and RBF decreased due to a vasoconstriction in M and R vasculature. These effects were attenuated by the
ganglion blocker
chlorisondamine (5 mg/kg, iv).
Anatoxin-A (100 micrograms/kg, iv) increased plasma
epinephrine levels by 2-fold with virtually no effect on
norepinephrine whereas
nicotine (100 micrograms/kg, iv) increased plasma
epinephrine and
norepinephrine by 20- to 30-fold. Central administration of
anatoxin-A and
nicotine (30-100 micrograms/kg icv) increased MAP with no effect on heart rate and produced M and R vasoconstriction. In summary, the present study demonstrates that
anatoxin-A acts as a
nicotinic cholinergic agonist in the conscious rat after both systemic and central administration.
Anatoxin-A and
nicotine produced pressor and reno-splanchnic
vasoconstrictor responses and at high doses increased cardiac output. These effects were mediated by activation of the
nicotinic receptors in the adrenal medulla and sympathetic ganglia. However, marked differences were found in the potency of
anatoxin-A versus
nicotine to stimulate the sympathoadrenomedullary axis.