Potentiation of the effects of atrial natriuretic factor on the cardiovascular system by amiloride.
Amiloride has previously been shown to facilitate receptor binding of atrial natriuretic factor (ANF) to membranes of adrenal cortex and to enhance ANF induced inhibition of steroid secretion in vitro. This interaction of amiloride and ANF also holds true for the cardiovascular system. In precontracted rabbit aortic strips the relaxing effect induced by the combination of ANF (10(-10) mol/l) and amiloride (10(-5) mol/l) was overadditional. The production of cyclic guanosine monophosphate (cGMP), which parallels ANF induced relaxations of vascular strips, was not affected by amiloride alone up to 10(-3) mol/l, but was concentration-dependently increased in the presence of ANF (10(-8) mol/l). In spontaneously hypertensive rats ANF-induced decreases in blood pressure were potentiated by amiloride. Post ischemia reperfusion arrhythmias in isolated rat hearts were reduced by ANF. Amiloride increased this effect. The binding experiments revealed an interaction of amiloride and ANF on the receptor level. Binding of labeled ANF to aortic tissue was concentration-dependently increased by amiloride. Addition of ATP had the opposite effect. Therefore it can be suggested that amiloride and ATP interfere with a mechanism regulating the sensitivity of the vascular ANF-receptor for its ligand regarding binding and signal transforming presumably by a kinase mediated phosphorylation/dephosphorylation process.
Albus
U
U
Hoechst Aktiengesellschaft, Frankfurt/Main, Fed. Rep. of Germany.
Linz
W
W
Wiemer
G
G
Knolle
J
J
Breipohl
G
G
Schölkens
B A
BA
D000584:Amiloride / Q000494:pharmacology*; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D004357:Drug Synergism; D005260:Female; D006321:Heart / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains
D000584:Amiloride; D009320:Atrial Natriuretic Factor; D000242:Cyclic AMP; D006152:Cyclic GMP