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 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 microg/kg). Relative to responses observed in CR, 5-HT at 10 microg/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 microg/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.
Araujo
M T
MT
Department of Physiological Sciences, Biomedical Center, Federal University of Espirito Santo, Vitoria, Brazil.
Barker
L A
LA
Cabral
A M
AM
Vasquez
E C
EC
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001919:Bradycardia; D003864:Depression, Chemical; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects*; D006973:Hypertension / Q000201:enzymology / Q000503:physiopathology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D012018:Reflex / Q000187:drug effects*; D012701:Serotonin / Q000494:pharmacology
D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D012701:Serotonin; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester