Differential inhibition of alpha-1 vs. alpha-2 adrenoceptor-mediated responses in canine saphenous vein by nitroglycerin.
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)
D000818:Animals; D001381:Azepines / Q000494:pharmacology; D004110:Diltiazem / Q000494:pharmacology; D004280:Dobutamine / Q000494:pharmacology; D004285:Dogs; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D005996:Nitroglycerin / Q000494:pharmacology*; D010643:Phenoxybenzamine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000145:classification / Q000187:drug effects*; D012501:Saphenous Vein / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects*
D001381:Azepines; D011942:Receptors, Adrenergic, alpha; D010643:Phenoxybenzamine; D010656:Phenylephrine; D004280:Dobutamine; C024763:talipexole; D004110:Diltiazem; D005996:Nitroglycerin