TY - JOUR
T1 - Flunarizine and α-adrenergic responses in isolated canine saphenous veins
AU - Daskalopoulos, Dimitris A.
AU - Rimele, Thomas J.
AU - Flavahan, Nicholas A.
AU - Vanhoutte, Paul M.
N1 - Funding Information:
Acknowledgements--The authors wish to thank Mrs Janet Beckman for secretarial assistance, and Mr Lawrence Aarhus and Mr Kevin Rud for excellent technical assistance. We would also like to thank the pharmaceutical companies mentioned under "Materials and Methods" for their generous gifts of drugs. This work was supported by part by NIH Research Grants HL 05883 and HL 07269 and by the Mayo Foundation.
PY - 1987
Y1 - 1987
N2 - 1. 1. Experiments were designed to determine how flunarizine affects contractions of cutaneous veins to α-adrenergic activation. 2. 2. Rings of canine saphenous vein were mounted at optimal length for isometric tension recording in organ chambers filled with physiological salt solution. 3. 3. At concentrations higher than those needed to inhibit KCl-induced contractions, flunarizine inhibited the contractile responses evoked by α2-adrenergic agonists (B-HT 920, xylazine), partial (St-587) and full (cirazoline, phenylephrine) α1-adrenergic agonists and the combined α1-/α2-adrenergic agonist, norepinephrine. 4. 4. The inhibitory effect of flunarizine against α2-adrenergic responses was similar to that produced by other calcium-antagonists and results presumably from inhibition of the influx of extracellular calcium. 5. 5. The inhibitory effect of flunarizine against α1-adrenergic responses was greater than expected and appears to result from competitive antagonism of α1-adrenoceptors (pA2 = 5.79). 6. 6. Therefore, flunarizine can decrease adrenergic contractile responses by depressing the influx of extracellular calcium and by blocking postjunctional α1-adrenoceptors.
AB - 1. 1. Experiments were designed to determine how flunarizine affects contractions of cutaneous veins to α-adrenergic activation. 2. 2. Rings of canine saphenous vein were mounted at optimal length for isometric tension recording in organ chambers filled with physiological salt solution. 3. 3. At concentrations higher than those needed to inhibit KCl-induced contractions, flunarizine inhibited the contractile responses evoked by α2-adrenergic agonists (B-HT 920, xylazine), partial (St-587) and full (cirazoline, phenylephrine) α1-adrenergic agonists and the combined α1-/α2-adrenergic agonist, norepinephrine. 4. 4. The inhibitory effect of flunarizine against α2-adrenergic responses was similar to that produced by other calcium-antagonists and results presumably from inhibition of the influx of extracellular calcium. 5. 5. The inhibitory effect of flunarizine against α1-adrenergic responses was greater than expected and appears to result from competitive antagonism of α1-adrenoceptors (pA2 = 5.79). 6. 6. Therefore, flunarizine can decrease adrenergic contractile responses by depressing the influx of extracellular calcium and by blocking postjunctional α1-adrenoceptors.
UR - http://www.scopus.com/inward/record.url?scp=0023136806&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0023136806&partnerID=8YFLogxK
U2 - 10.1016/0306-3623(87)90249-7
DO - 10.1016/0306-3623(87)90249-7
M3 - Article
C2 - 2883070
AN - SCOPUS:0023136806
SN - 0306-3623
VL - 18
SP - 193
EP - 196
JO - General Pharmacology
JF - General Pharmacology
IS - 2
ER -