A possible change in the rate-limiting step for cardiac norepinephrine synthesis in the cardiomyopathic Syrian hamster

The development of heart failure in the cardiomyopathic hamster is associated with a decrease in norepinephrine stores and parallel increases in cardiac sympathetic tone and tyrosine hydroxylase activity. Despite the increase in tyrosine hydroxylase, cardiac norepinephrine synthesis does not increas...

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Veröffentlicht in:Circulation research 1977-12, Vol.41 (6), p.814-817
Hauptverfasser: Sole, M J, Kamble, A B, Hussain, M N
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container_title Circulation research
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creator Sole, M J
Kamble, A B
Hussain, M N
description The development of heart failure in the cardiomyopathic hamster is associated with a decrease in norepinephrine stores and parallel increases in cardiac sympathetic tone and tyrosine hydroxylase activity. Despite the increase in tyrosine hydroxylase, cardiac norepinephrine synthesis does not increase in heart failure. In this study, we have shown that an accumulation of cardiac dopamine accompanies the decline of cardiac norepinephrine. The abnormal content of norepinephrine and of dopamine in the decompensating hamster heart is restored to normal by peripheral ganglionic blockade. The acute increase in cardiac sympathetic tone induced by immobilization stress in control hamsters mimics the alterations in cardiac catecholamine distribution found in heart failure. Other investigators have demonstrated similar alterations in the catecholamine content of the rat submaxillary gland and adrenal medulla following an increase in sympathetic input to these organs. We conclude that the increase in cardiac sympathetic tone in the late stages of hamster cardiomyopathy appears to lead to a shift in the rate-limiting step for norepinephrine synthesis from the hydroxylation of tyrosine to the hydroxylation of dopamine. There is evidence that this shift which results in an accumulation of dopamine in the noradrenergic nerve terminals of the heart is a general manifestaion of augmented sympathetic nerve traffic rather than a peculiarity of hamster cardiomyopathy.
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We conclude that the increase in cardiac sympathetic tone in the late stages of hamster cardiomyopathy appears to lead to a shift in the rate-limiting step for norepinephrine synthesis from the hydroxylation of tyrosine to the hydroxylation of dopamine. 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We conclude that the increase in cardiac sympathetic tone in the late stages of hamster cardiomyopathy appears to lead to a shift in the rate-limiting step for norepinephrine synthesis from the hydroxylation of tyrosine to the hydroxylation of dopamine. 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source MEDLINE; American Heart Association Journals; Journals@Ovid Complete; EZB-FREE-00999 freely available EZB journals
subjects Animals
Cardiomyopathies - complications
Cardiomyopathies - physiopathology
Catecholamines
Chemical Phenomena
Chemistry
Chlorisondamine - pharmacology
Cricetinae
Dopamine
Heart
Heart Failure - complications
Mesocricetus
Norepinephrine - biosynthesis
Sympathetic Nervous System - physiopathology
Tyrosine 3-Monooxygenase
title A possible change in the rate-limiting step for cardiac norepinephrine synthesis in the cardiomyopathic Syrian hamster
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