Low-dose endothelin-1 potentiates volume-induced secretion of atrial natriuretic factor.
To evaluate the role of calcium in volume-induced secretion of atrial natriuretic factor (ANF), effects of verapamil and endothelin-1 (ET-1), both known to influence free intracellular calcium, were studied during saline infusion in seven conscious instrumented dogs. Fifteen minutes after intravenous injection of placebo or verapamil (0.25 mg/kg) or during continuous ET-1 infusion (at 5 ng.kg-1.min-1), saline (10% body wt) was infused during 40 min. Saline produced a rise (P less than 0.001) of plasma ANF from 28.1 +/- 6.3 to 50.4 +/- 12.9 pM after placebo, from 30.2 +/- 6.1 to 51.1 +/- 8.5 pM after verapamil, and from 31.2 +/- 6.1 to 81.0 +/- 12.9 pM with ET-1. This increase was comparable after placebo and verapamil, but was 80% greater with ET-1 (P less than 0.02). Plasma ET-1, unchanged after placebo, rose (P less than 0.001) from 1.7 +/- 0.5 to 38.3 +/- 9.2 pM with ET-1. In the three experiments, heart rate and left atrial pressure (LAP) increased (P less than 0.001) similarly. The linear relation between ANF and LAP was steeper with ET-1 than with saline or verapamil (both P less than 0.05), indicating that the enhanced ANF secretion with ET-1 was occurring at all levels of LAP. Thus volume-induced secretion of ANF is not suppressed by verapamil, but is directly enhanced by low-dose ET-1, known to activate the phosphoinositide pathway.
Donckier
J
J
Division of Endocrinology, University Hospital Université Catholique de Louvain of Mont-Godinne, Yvoir, Belgium.
Hanet
C
C
Galanti
L
L
Stoleru
L
L
Van Mechelen
H
H
Robert
A
A
Ketelslegers
J M
JM
Pouleur
H
H
D000804:Angiotensin II / Q000097:blood; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000097:blood / Q000378:metabolism*; D001810:Blood Volume / Q000502:physiology*; D002319:Cardiovascular System / Q000187:drug effects; D002395:Catecholamines / Q000097:blood; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D016232:Endothelins / Q000008:administration & dosage* / Q000097:blood / Q000494:pharmacology; D006321:Heart / Q000502:physiology; D006325:Heart Atria; D011312:Pressure; D014700:Verapamil / Q000008:administration & dosage / Q000494:pharmacology
D002395:Catecholamines; D016232:Endothelins; D000804:Angiotensin II; D009320:Atrial Natriuretic Factor; D014700:Verapamil