title: Cardiovascular effects of anatoxin-A in the conscious rat.
abstract: 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.
authors.affiliation: Department of Neurology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814.
authors.forename: A L
authors.initials: AL
authors.lastname: Sirén
authors.forename: G
authors.initials: G
authors.lastname: Feuerstein
mesh_terms: D000818:Animals; D001427:Bacterial Toxins; D002302:Cardiac Output / Q000187:drug effects / Q000502:physiology; D002320:Cardiovascular Physiological Phenomena; D002319:Cardiovascular System / Q000187:drug effects*; D002395:Catecholamines / Q000097:blood; D000458:Cyanobacteria; D000087522:Cyanobacteria Toxins; D006614:Hindlimb / Q000098:blood supply; D007276:Injections, Intraventricular; D008297:Male; D008387:Marine Toxins / Q000494:pharmacology*; D052998:Microcystins; D009538:Nicotine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D012079:Renal Circulation / Q000187:drug effects / Q000502:physiology; D013152:Splanchnic Circulation / Q000187:drug effects / Q000502:physiology; D014326:Tropanes; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology; D014851:Wakefulness / Q000187:drug effects* / Q000502:physiology
chemical_list: D001427:Bacterial Toxins; D002395:Catecholamines; D000087522:Cyanobacteria Toxins; D008387:Marine Toxins; D052998:Microcystins; D014326:Tropanes; D009538:Nicotine; C509783:anatoxin a