Developmental conversion of inotropism by endothelin I and angiotensin II from positive to negative in mice.
Inotropic effects on isolated neonatal and adult mouse myocardium of endothelin I and angiotensin II were examined. Endothelin I produced a sustained positive inotropic response in the neonate but a sustained negative response in the adult. Both were concentration-dependent and were inhibited by the endothelin ETA receptor antagonist, BQ-123 (Cyclo(D-a-aspartyl-L-prolyl-D-valyl-L-leucyl-D-tryptophyl)). Angiotensin II produced a sustained positive inotropic response in the neonate while a sustained negative response in the adult. Both were concentration-dependent and were inhibited by the angiotensin AT1 receptor antagonist, YM358 (2,7-diethyl-5-((2'-(1 H-tetrazol-5-yl)biphenyl-4-yl)methyl-5H-pyrazolo(1,5-b)(1,2,4)tria zole potassium salt monohydrate). These results indicate that inotropic responses of the mouse heart to cardioactive peptides are unique among experimental animal species and may be reversed during development.
Sekine
T
T
Department of Pharmacology, Toho University School of Pharmaceutical Sciences, Chiba, Japan.
Kusano
H
H
Nishimaru
K
K
Tanaka
Y
Y
Tanaka
H
H
Shigenobu
K
K
D000367:Age Factors; D000804:Angiotensin II / Q000494:pharmacology*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000831:Animals, Newborn; D000959:Antihypertensive Agents / Q000494:pharmacology; D001393:Azoles / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000494:pharmacology*; D006352:Heart Ventricles / Q000187:drug effects; D066298:In Vitro Techniques; D051379:Mice; D009200:Myocardial Contraction / Q000187:drug effects*; D010456:Peptides, Cyclic / Q000494:pharmacology; D044022:Receptor, Endothelin A; D016276:Ventricular Function
D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D001393:Azoles; D001713:Biphenyl Compounds; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D010456:Peptides, Cyclic; D044022:Receptor, Endothelin A; C105489:YM358; D000804:Angiotensin II; C072247:cyclo(Trp-Asp-Pro-Val-Leu)