TY - JOUR
T1 - Nisoldipine inhibits adrenergic responses in the hindquarters vascular bed of the cat
AU - Minkes, Robert K.
AU - Bellan, John A.
AU - Kerstein, Morris D.
AU - McNamara, Dennis B.
AU - Kadowitz, Philip J.
PY - 1989/6/20
Y1 - 1989/6/20
N2 - The effects of the calcium entry blocking agent nisoldipine on adrenergic vasoconstrictor responses were investigated in the hindquarters vascular bed of the cat under conditions of controlled blood flow. Nisoldipine dilated the hindquarters vascular bed and inhibited vasoconstrictor responses to Bay K 8644, a nifedipine analog which promotes calcium entry. During infusion of nisoldipine, vasoconstrictor responses to sympathetic nerve stimulation, norepinephrine, and tyramine were inhibited in a reversible manner. In addition to blocking responses to nerve-released and exogenous norepinephrine, the calcium entry antagonist decreased responses to methoxamine and BHT 933, α1- and α2-adrenoceptor agonists. Responses to methoxamine were reduced by prazosin, an α1-adrenoceptor antagonist, but not by yohimbine, an α2-adrenoceptor blocking agent, whereas responses to BHT 933 were decreased by yohimbine but not by prazosin. The results of these studies suggest that vasoconstrictor responses to neuronally released and exogenous norepinephrine, as well as to selective α1- and α2-adrenoceptor agonists, are dependent in part on an extracellular source of calcium in resistance vessels of the feline hindquarters vascular bed. The inhibitory effect of nisoldipine on vasoconstrictor responses to neuronally released norepinephrine may be important in the antihypertensive actions of calcium entry blocking agents.
AB - The effects of the calcium entry blocking agent nisoldipine on adrenergic vasoconstrictor responses were investigated in the hindquarters vascular bed of the cat under conditions of controlled blood flow. Nisoldipine dilated the hindquarters vascular bed and inhibited vasoconstrictor responses to Bay K 8644, a nifedipine analog which promotes calcium entry. During infusion of nisoldipine, vasoconstrictor responses to sympathetic nerve stimulation, norepinephrine, and tyramine were inhibited in a reversible manner. In addition to blocking responses to nerve-released and exogenous norepinephrine, the calcium entry antagonist decreased responses to methoxamine and BHT 933, α1- and α2-adrenoceptor agonists. Responses to methoxamine were reduced by prazosin, an α1-adrenoceptor antagonist, but not by yohimbine, an α2-adrenoceptor blocking agent, whereas responses to BHT 933 were decreased by yohimbine but not by prazosin. The results of these studies suggest that vasoconstrictor responses to neuronally released and exogenous norepinephrine, as well as to selective α1- and α2-adrenoceptor agonists, are dependent in part on an extracellular source of calcium in resistance vessels of the feline hindquarters vascular bed. The inhibitory effect of nisoldipine on vasoconstrictor responses to neuronally released norepinephrine may be important in the antihypertensive actions of calcium entry blocking agents.
KW - Adrenergic responses
KW - Nisoldipine
KW - Vascular bed (hindquarters)
KW - α-Adrenoceptors
KW - α-Adrenoceptors
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U2 - 10.1016/0014-2999(89)90720-6
DO - 10.1016/0014-2999(89)90720-6
M3 - Article
C2 - 2476323
AN - SCOPUS:0024370680
SN - 0014-2999
VL - 165
SP - 259
EP - 267
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
IS - 2-3
ER -