Differential inhibition of alpha-1 vs. alpha-2 adrenoceptor-mediated responses in canine saphenous vein by nitroglycerin. J Pharmacol Exp Ther 1986 Aug;238(2):515-21
Date
08/01/1986Pubmed ID
3016240Scopus ID
2-s2.0-0022458441 (requires institutional sign-in at Scopus site) 8 CitationsAbstract
In the present investigation, the subtype of alpha adrenoceptor that is preferentially antagonized by the noncalcium entry blocker, nitroglycerin (GTN), was studied in vitro using rings prepared from isolated canine saphenous vein (CSV). The calcium entry blocker, diltiazem (DZ), was used for purposes of comparison. Contractions were produced by the following alpha adrenergic agonists: norepinephrine (NE), a nonselective alpha adrenoceptor agonist, phenylephrine (PE), a selective alpha-1 adrenoceptor agonist and B-HT 920, a selective alpha-2 adrenoceptor agonist. The inhibitory effects of GTN on contractions produced by submaximal concentrations (EC65 to EC75) of NE, PE and B-HT 920 were determined. GTN was found to inhibit preferentially the postsynaptic alpha-2 adrenoceptor-mediated responses to B-HT 920 while producing minimal effects on those produced by NE or PE. Similar results were found with DZ. However, when a portion of the alpha-1 adrenoceptor pool was inactivated by phenoxybenzamine (5 X 10(-8) to 1 X 10(-7) M), GTN and DZ both produced a significant depression of responses to PE, a full alpha-1 adrenoceptor agonist. In addition, contractions produced by l-dobutamine, a selective partial alpha-1 adrenoceptor agonist (no alpha receptor reserve), were highly sensitive to inhibition by GTN. These results suggest that the selective inhibition of contractions mediated by postjunctional alpha-2 vs. alpha-1 adrenoceptors in CSV by GTN and DZ may be due partially to the presence of a large alpha-1 adrenoceptor reserve that conceals an underlying functional antagonism to alpha-1 adrenoceptor-mediated responses.(ABSTRACT TRUNCATED AT 250 WORDS)
Author List
Eskinder H, Gross GJMESH terms used to index this publication - Major topics in bold
AnimalsAzepines
Diltiazem
Dobutamine
Dogs
Female
In Vitro Techniques
Male
Nitroglycerin
Phenoxybenzamine
Phenylephrine
Receptors, Adrenergic, alpha
Saphenous Vein
Vasoconstriction
