Propranolol and atenolol inhibit norepinephrine spillover rate into plasma in conscious spontaneously hypertensive rats.
Radiotracer techniques capable of measuring norepinephrine clearance and spillover rate into plasma were used to test the hypothesis that the antihypertensive effects of propranolol and atenolol in conscious spontaneously hypertensive rats are associated with an inhibition of norepinephrine release from postganglionic sympathetic neurons. The 10%-15% fall in mean arterial pressure produced over 4 h by propranolol (1, 3.3 and 10 mg/kg, s.c.) and atenolol (1, 3.3 and 10 mg/kg, s.c.) was not dose-related, and only the largest dose of propranolol caused a significant bradycardia. Each dose of atenolol significantly lowered heart rate. The decrease in blood pressure caused by propranolol and atenolol was not related to the decrease in heart rate. Both propranolol and atenolol inhibited norepinephrine clearance by 12% to 16%. The 1 mg/kg doses of propranolol and atenolol significantly suppressed norepinephrine spillover rate by 21% and 32%, respectively, at 4 h postinjection. As the dose of propranolol was increased, the inhibition of norepinephrine spillover was reversed as plasma epinephrine concentration rose by 125%. The suppression of norepinephrine spillover rate caused by atenolol was more persistent but did diminish after the 10 mg/kg dose, when plasma epinephrine concentration was elevated by 55%. Both drugs suppressed plasma renin concentration, but the inhibition of norepinephrine spillover rate by propranolol and atenolol was not related to the fall in plasma renin concentration. By comparison, treatment with the adrenergic neuron blocking agent bretylium (5, 10, 20 and 40 mg/kg, s.c.) elicited a dose-related vasodepression with no change in heart rate or plasma renin concentration.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Pharmacology, University of Texas Health Science Center, San Antonio 78284-7764.
T K
TK
Keeton
A M
AM
Biediger
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001262:Atenolol / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D001949:Bretylium Compounds / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000097:blood / Q000378:metabolism; D008297:Male; D009638:Norepinephrine / Q000097:blood* / Q000493:pharmacokinetics; D011433:Propranolol / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D013564:Sympathetic Nervous System / Q000378:metabolism
D000319:Adrenergic beta-Antagonists; D001949:Bretylium Compounds; D001262:Atenolol; D011433:Propranolol; C045166:bretylium; D009638:Norepinephrine; D004837:Epinephrine