Nisoldipine inhibits adrenergic responses in the hindquarters vascular bed of the cat.
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, alpha 1- and alpha 2-adrenoceptor agonists. Responses to methoxamine were reduced by prazosin, an alpha 1-adrenoceptor antagonist, but not by yohimbine, an alpha 2-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 alpha 1- and alpha 2-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.
Minkes
R K
RK
Department of Pharmacology, Tulane University School of Medicine, New Orleans, LA 70112.
Bellan
J A
JA
Kerstein
M D
MD
McNamara
D B
DB
Kadowitz
P J
PJ
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002415:Cats; D004347:Drug Interactions; D005260:Female; D006614:Hindlimb / Q000098:blood supply*; D008297:Male; D009121:Muscle Denervation; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000494:pharmacology; D015737:Nisoldipine; D009638:Norepinephrine / Q000494:pharmacology; D012039:Regional Blood Flow / Q000187:drug effects; D013564:Sympathetic Nervous System / Q000187:drug effects*
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D002121:Calcium Channel Blockers; D015737:Nisoldipine; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D009543:Nifedipine; D009638:Norepinephrine