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 Nω-nitro- -arginine methyl ester (L-NAME, averaging 35 mg/kg/day), for 3, 6, and 12 days (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 μg/kg). Relative to responses observed in CR, 5-HT at 10 μg/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 μg/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.