Cardiovascular effects of nonivamide succinate

Intravenous injection of nonivamide or nonivamide succinate (25, 250 nmol/kg) into Wistar rats induced bradycardia, hypotension, apnea and a triphasic blood pressure response: an initial short fall (effect A), an intermediate rise (effect B), and a subsequent delayed fall (effect C) of blood pressure. This blood pressure response remained unchanged after treatment with propranolol or phentolamine. In atropine-pretreatment rats the initial effect A was markedly decreased and effect C was slight increased. Effect A was absent after bilateral vagotomy. Unilateral microinjection of nonivamide succinate (3, 30 fmol) into the nucleus tractus solitarii produced a marked reduction in blood pressure and heart rate. In the isolated aorta of the guinea pig, application of either nonivamide or its succinate (10(-8) to 10(-5) M) eliminated the smooth muscle tone produced by phenylephrine (10(-6) M). Re-exposure to these agents, however, produced an immediate tachyphylactic relaxing response and prolonged rebound contractile response. Both compounds induced a vascular contraction rather than relaxation during tachyphylaxis. The potency of nonivamide succinate was found to be slightly greater than that of nonivamide.