Korean J Anesthesiol.  1999 Oct;37(4):694-703. 10.4097/kjae.1999.37.4.694.

Effects of Amrinone on the Vascular Tension of the Isolated Rabbit Pulmonary Artery

• Cho SY
• Suh JK
• Shin WJ
• Yeom JH
• Oh MK
• Kim KH
• Yoo HK

• KMID: 2091473
• DOI: http://doi.org/10.4097/kjae.1999.37.4.694

Abstract

BACKGROUND: Amrinone is a noncatecholamine, nonglycoside compound, which is known to possess both cardiac inotropic and vasodilatory actions. This drugs has been increasingly used in clinical practice for the management of low cardiac output syndrome during anesthesia, particularly for patients associated with right heart failure and pulmonary hypertension. The aim of this study was to explore the direct vasoactive effect of amrinone and its action mechanisms in the isolated rabbit pulmonary artery.
METHODS
The rabbits' pulmonary arteries were dissected free and cut into rings (3 4 mm) and mounted for isometric tension in a tissue chamber. The effects of amrinone (5 10 6 5 10 4 M) on the vascular tension were assessed in the by KCl (40 mM)- or norepinephrine (NE, 10 6 M)- precontracted pulmonary arterial rings with or without endothelium. Also effects of K channel blockers (tetraethyl ammonium 20 mM, glybenclamide 2.5 10 5 M, 4-aminopyridine (4-AP) 5 10 4 M), protein kinase A & G inhibitor (H8), L-NAME, methylene blue and indomethacin on the amrinone- induced vascular responses were investigated. Also studied was effects of amrinone on the Ca2 influx through voltage operated channel (VOC) and receptor operated channel (ROC) of the vascular cells.
RESULTS
Amrinone produced vasorelaxation of KCl- or NE-precontracted pulmonary artery in a dose-dependent fashion. The amrinone-induced vasorelaxation was not affected by the denudation of the endothelium. Pretreatment with L-NAME and methylene blue did not affect the vasodilatory effect of amrinone, suggesting that nitric oxide is not involved. Following pretreatment with indomethacin (a cyclooxygenase inhibitor) or K channel blockers, the amrinone-induced vasorelaxation was not altered. After exposure to Ca2 free solution, amrinone attenuated the KCl- or NE-induced contraction even in the presence of Ca2 , implying that VOC and ROC are blocked by amrinone. On the other hand, protein kinase A blocker (H8) completely abolished the amrinone-induced relaxation in the KCl-precontracted pulmonary artery.
CONCLUSIONS
These findings suggest that the amrinone-induced vasorelaxations result from inhibition of VOC and ROC as well as from the activation of protein kinase A in the isolated rabbit pulmonary artery.

Keyword

Arteries, rabbit pulmonary artery; Ion channel, Ca2 channel, K channel; Pharmacology, amrinone, L-nitro arginine methyl ester, indomethacin, methylene blue, tetraethyl ammonium, glybenclamide, H8

MeSH Terms

4-Aminopyridine
Ammonium Compounds
Amrinone*
Anesthesia
Cardiac Output, Low
Cyclic AMP-Dependent Protein Kinases
Endothelium
Glyburide
Hand
Heart Failure
Humans
Hypertension, Pulmonary
Indomethacin
Methylene Blue
NG-Nitroarginine Methyl Ester
Nitric Oxide
Norepinephrine
Prostaglandin-Endoperoxide Synthases
Pulmonary Artery*
Relaxation
Vasodilation
4-Aminopyridine
Amrinone
Cyclic AMP-Dependent Protein Kinases
Glyburide
Indomethacin
Methylene Blue
NG-Nitroarginine Methyl Ester
Nitric Oxide
Norepinephrine
Prostaglandin-Endoperoxide Synthases