title: Effects of PN 200-110, a new calcium antagonist, on alpha 1- and alpha 2-adrenoceptor mediated vasoconstriction elicited by selective alpha-adrenoceptor agonists and catecholamines in the pithed rat.
abstract: The inhibitory action of PN 200-110, a novel calcium antagonist, on alpha 1- and alpha 2-adrenoceptor mediated pressor effects elicited by selective alpha-adrenoceptor agonists and catecholamines was studied in pithed rats. The pressor effects of the selective alpha 1-adrenoceptor agonist cirazoline were only slightly influenced by PN 200-110 (0.1 mg/kg). On the other hand, PN 200-110 efficiently inhibited the hypertensive effects of the selective alpha 2-adrenoceptor agonist B-HT 920 in a dose-dependent way, thereby reducing the maximal response considerably (pD2' = 7.30). The alpha 1-adrenoceptor mediated pressor responses of adrenaline and noradrenaline, obtained after pretreatment with propranolol and the selective alpha 2-adrenoceptor antagonist yohimbine, were slightly inhibited by PN 200-110, without influencing maximal responses. PN 200-110 inhibited the alpha 1-adrenergic pressor effects of noradrenaline better than those of adrenaline. The alpha 2-adrenoceptor mediated pressor effects of the cathecholamines obtained after pretreatment with propranolol and the selective alpha 1-adrenoceptor antagonist prazosin, were highly susceptible to blockade by PN 200-110 except for the high doses (300 micrograms/kg) of adrenaline. The present study establishes the pronounced calcium entry inhibitory potency of PN 200-110 and confirms and extends previous observations that blockade of calcium entry preferably impairs alpha 2-adrenoceptor mediated vasoconstriction in vivo, when compared to that elicited by alpha 1-adrenoceptor stimulation.
authors.forename: K
authors.initials: K
authors.lastname: Jie
authors.forename: P
authors.initials: P
authors.lastname: van Brummelen
authors.forename: P B
authors.initials: PB
authors.lastname: Timmermans
authors.forename: M J
authors.initials: MJ
authors.lastname: Thoolen
authors.forename: P A
authors.initials: PA
authors.lastname: van Zwieten
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D001381:Azepines / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002395:Catecholamines / Q000494:pharmacology*; D003655:Decerebrate State; D004837:Epinephrine / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D017275:Isradipine; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D010069:Oxadiazoles / Q000494:pharmacology*; D011224:Prazosin / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D000316:Adrenergic alpha-Agonists; D001381:Azepines; D002121:Calcium Channel Blockers; D002395:Catecholamines; D007093:Imidazoles; D010069:Oxadiazoles; D011942:Receptors, Adrenergic, alpha; C024763:talipexole; D011433:Propranolol; C014282:cirazoline; D009638:Norepinephrine; D011224:Prazosin; D004837:Epinephrine; D017275:Isradipine