title: Vasoactive agonists prevent erythrocyte extravasation in thrombocytopenic hamsters.
abstract: The mediating action of selected vasoactive amines and their respective antagonists on vascular fragility, visible as cutaneous petechiae, was assayed with thrombocytopenic (TCP) hamsters. Serotonin (5-HT), norepinephrine (NE), epinephrine, dopamine and isoproterenol administered IP reduced petechiae significantly within 10 min; phenylephrine had no effect. Of the natural amines, 5-HT and NE were most effective in reducing petechial sensitivity to values obtained with untreated, normal animals; hence these two amines only were tested pharmacologically. Pretreatment of TCP animals with Ketanserin or propranolol, administered IP or IV, abolished any petechial inhibitory action of 5-HT and NE respectively; pretreatment with phenoxybenzamine reduced significantly the NE inhibition of petechiae, but to a lesser degree than propranolol. In contrast, atenolol, prazosin and yohimbine had no significant effect. Ketanserin abolished the action of NE, but adrenoceptor blockers had no effect on 5-HT-treated TCP hamsters. The results suggest that 5-HT and NE inhibition of petechiae may be receptor-mediated and that there may be receptor interaction. This was supported by the observation that non-additive subthreshold doses of 5-HT and NE, which individually did not prevent petechial formation in TCP hamsters, when combined totally inhibited petechiae. The theorized importance of endogenous 5-HT and NE to maintain postcapillary venule junctional integrity (site of petechial hemorrhaging) was also demonstrated by treating normal hamsters with drugs known to block or antagonize either 5-HT or NE uptake. In every instance petechial sensitivity rapidly occurred, and the loss of microvascular integrity in Ketanserin-treated hamsters mimicked quantitatively the petechial sensitivity observed with TCP animals.
mesh_terms: D000818:Animals; D002198:Capillary Fragility / Q000187:drug effects*; D002199:Capillary Permeability / Q000187:drug effects*; D006224:Cricetinae; D004298:Dopamine / Q000494:pharmacology*; D004837:Epinephrine / Q000494:pharmacology*; D004912:Erythrocytes / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology*; D010656:Phenylephrine / Q000494:pharmacology; D010976:Platelet Count; D011941:Receptors, Adrenergic / Q000187:drug effects; D011985:Receptors, Serotonin / Q000187:drug effects; D012701:Serotonin / Q000494:pharmacology*; D013921:Thrombocytopenia / Q000097:blood / Q000188:drug therapy*
chemical_list: D011941:Receptors, Adrenergic; D011985:Receptors, Serotonin; D010656:Phenylephrine; D012701:Serotonin; D007545:Isoproterenol; D004298:Dopamine; D009638:Norepinephrine; D004837:Epinephrine