Effects of human ANF-(99-126) on sympathetic nerve function, hemodynamic parameters and plasma cGMP levels in anesthetized, ganglion-blocked dogs.
The ability of human ANF-(99-126) (ANF) to affect neuronal function, plasma cGMP levels or various hemodynamic parameters was tested in anesthetized dogs subjected to ganglionic blockade which prevented reflex changes in sympathetic tone. In each group of dogs, heart rate changes due to electrical stimulation of the cardioaccelerator nerve at 0.5, 1, 3 and 10 Hz were measured before and after ANF or vehicle infusion. A possible direct effect of ANF on the beta-adrenoceptor mechanisms was assessed by evaluating changes in heart rate after i.v. administration of isoproterenol (a beta-adrenoceptor agonist). The results showed that i.v. infusion of ANF (200 pmol/kg per min for 60 min), but not vehicle, produced significant inhibition of heart rate responses to low frequency nerve stimulation (0.5-1 Hz) when compared to vehicle 30 min after the end of infusion; high frequency (10 Hz) responses remained unaffected. A significant (P less than 0.05) enhancement in isoproterenol responses was evident in ANF-treated animals at the end of infusion, and 30 min afterward. ANF increased plasma cGMP from pretreatment levels of 28 +/- 4 to 149 +/- 1 pmol/ml at the end of infusion, and falling to 63 +/- 7 pmol/ml 30 min later (t 1/2 = 25.1 +/- 2.2 min). Cardiac output also tended to fall during infusion and remained significantly reduced (-18%) 30 min after infusion's end; blood pressure fell without a decrease in total peripheral resistance. Thus, ANF produced a direct, frequency-dependent depressant action on sympathetic nerve function, reduced both cardiac output and blood pressure, and enhanced chronotropic responses to beta-adrenoceptor stimulation. These persistent changes in hemodynamic parameters and neuronal function may contribute to the mechanism of action of ANF.
Bergey
J L
JL
Squibb Institute for Medical Research, Princeton, NJ 08543-4000.
Much
D R
DR
Kratunis
V
V
Asaad
M
M
D000758:Anesthesia; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D006152:Cyclic GMP / Q000097:blood*; D004285:Dogs; D005730:Ganglionic Blockers / Q000494:pharmacology*; D006321:Heart / Q000294:innervation; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D010446:Peptide Fragments / Q000494:pharmacology*; D011943:Receptors, Adrenergic, beta / Q000502:physiology; D013564:Sympathetic Nervous System / Q000187:drug effects*; D014655:Vascular Resistance / Q000187:drug effects
D005730:Ganglionic Blockers; D010446:Peptide Fragments; D011943:Receptors, Adrenergic, beta; D009320:Atrial Natriuretic Factor; D006152:Cyclic GMP