Reflex pressor response to arterial phenylbiguanide: role of abdominal sympathetic visceral afferents

Phenylbiguanide (PBG), a 5-HT(3) (serotonin) receptor agonist, has been used in many studies as a "selective" agonist to elicit reflex bradycardia and hypotension through activation of cardiac and pulmonary vagal afferents. Because we have shown that endogenous 5-HT stimulates ischemically sensitive abdominal sympathetic afferents through 5-HT(3) receptors, we investigated the possibility that left ventricular (LV) and intra-arterial administration of PEG may evoke a competing reflex response by increasing the activity of sympathetic visceral afferents in anesthetized cats. Mean arterial pressure (MAP) and heart rate (KR) were monitored. When both vagal and sympathetic afferents were intact, PEG (40 mu g/kg, injected into the LV) significantly decreased MAP and HR in 8 of 10 cats but increased MAP in the remaining 2 cats. After bilateral cervical vagotomy, LV PEG significantly increased MAP. PEG (40 mu g/kg ia) significantly increased MAP and HR, whereas intravenous PEG significantly decreased MAP and HR (n = 10 cats). Furthermore, the presser response to PEG (40 mu g/kg ia) was reduced by 68% (P < 0.05; n = 4 cats) by celiac and mesenteric ganglionectomies. In studies of single-unit abdominal sympathetic afferents, intra-arterial but not intravenous PEG (40 mu g/kg) significantly increased activity of 10 ischemically sensitive afferents but not ischemically insensitive afferents. Blockade of 5-HT(3) receptors with tropisetron (200 mu g/kg iv) eliminated the response of the afferents and the presser response to PEG. These data indicate that PEG administered into the LV usually, but not always, evokes a depressor response that is converted to a presser response following cervical vagotomy. Also, intra-arterial PEG induces a presser response by stimulating 5-HT(3) receptors largely associated with ischemically sensitive abdominal sympathetic afferents.