Inhibition of nitric oxide synthase causes profound enhancement of the Bezold-Jarisch reflex

The Bezold-Jarisch reflex function was evaluated in rats made hypertensive by the chronic oral intake of a nitric oxide synthase inhibitor N-omega-nitro-L-arginine methyl est er (L-NAME, averaging 35 mg/kg/day), for 3, 6, and 12 clays (n = 9/group) and in untreated control rats (CR, n = 9/group). L-NAME-treated rats showed a marked hypertension (MAP: 148 +/- 3, 182 +/- 4, and 179 +/- 4 mm Hg, respectively) compared with CR (110 +/- 2 mm Hg). The 6- and 12-day groups showed tachycardia (447 +/- 20 and 466 +/- 13 beats/min, respectively) when compared with CR (355 +/- 10 beats/min), When compared with CR, left ventricular hypertrophy was observed in rats treated with L-NAME for 6 and 12 days. The Bezold-Jarisch reflex, a decrease in heart rate (HR) accompanied by a decrease in diastolic arterial pressure (DAP), was evoked in a dose dependent manner by the intravenous injection of 5-hydroxytryptamine (5-HT, 5 to 10 mu g/kg), Relative to responses observed in CR, 5-HT at 10 mu g/kg caused a four-to fivefold greater decrease in HR and a two-to threefold greater decrease in DAP in all the L-NAME treatment groups, Using a Langendorff technique, we observed a significant increase in the responsiveness of the pacemaker to acetylcholine (1.25 to 80 mu g/mL). These data suggest that the pharmacological inhibition of the nitric oxide synthase causes profound changes in the mechanisms of cardiovascular regulation as shown by a marked enhancement of the Bezold-Jarisch reflex in L-NAME-treated rats. The enhancement of this reflex seems to be in great part due to the hyperresponsiveness of the cardiac pacemaker to cholinergic stimulation. (C) 1998 American Journal of Hypertension, Ltd.