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MECHANISMS OF THE EFFECTS OF ENDOTHELIN ON RESPONSES TO NORADRENALINE AND SYMPATHETIC NERVE STIMULATION
Author(s) -
WongDusting H. K.,
La M.,
Rand M. J.
Publication year - 1990
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.1990.tb01319.x
Subject(s) - endocrinology , medicine , stimulation , protein kinase c , extracellular , vasoconstriction , calcium , chemistry , endothelin receptor , phorbol , calcium in biology , endothelin 1 , receptor , kinase , biochemistry
SUMMARY 1. The effects of endothelin (0.1–1 nmol/L) and the phorbol ester, phorbol 12‐myristate 13‐acetate (PMA, 0.1–100 nmol/L) have been studied on vasoconstrictor responses to sympathetic nerve stimulation and noradrenaline in the rabbit isolated ear artery. 2. Endothelin (0.1 nmol/L) significantly enhanced the biphasic response of the arteries to a prolonged period of sympathetic nerve stimulation (2 Hz for 60 s). Both the component of the response attributable to mobilization of intracellular calcium (phasic response) and the component due to the influx of extracellular calcium (tonic response) were enhanced. 3. PMA (0.1 and 0.3 nmol/L), which activates protein kinase C, enhanced vasoconstrictor responses to noradrenaline but a higher concentration of PMA (100 nmol/L) inhibited responses to noradrenaline. 4. It is concluded that the enhancement of responses to sympathetic nerve stimulation and noradrenaline produced by endothelin may be due to facilitation of the influx of extracellular calcium and to the activation of protein kinase C.