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CLINICAL STUDIES: CARDIAC PHYSIOLOGY

Baroreceptor dysfunction induced by nitric oxide synthase inhibition in humans

^a Department of Cardiology, University Hospital, Zürich, Switzerland

Manuscript received August 5, 1999; revised manuscript received December 30, 1999, accepted February 28, 2000.

Reprint requests and correspondence: Dr. Georg Noll, Cardiology, University Hospital, CH-8091 Zürich, Switzerland
karnog{at}usz.unizh.ch

OBJECTIVES

We sought to investigate baroreceptor regulation of sympathetic nerve activity and hemodynamics after inhibition of nitric oxide (NO) synthesis.

BACKGROUND

Both the sympathetic nervous system and endothelium-derived substances play essential roles in cardiovascular homeostasis and diseases. Little is known about their interactions.

METHODS

In healthy volunteers, we recorded muscle sympathetic nerve activity (MSA) with microneurography and central hemodynamics measured at different levels of central venous pressure induced by lower body negative pressure.

RESULTS

After administration of the NO synthase inhibitor N^G-monomethyl-L-arginine (L-NMMA, 1 mg/kg/min), systolic blood pressure increased by 24 mm Hg (p = 0.01) and diastolic blood pressure by 12 mm Hg (p = 0.009), while stroke volume index (measured by thermodilution) fell from 53 to 38 mL/min/m² (p < 0.002). Administration of L-NMMA prevented the compensatory increase of heart rate, but not MSA, to orthostatic stress. The altered response of heart rate was not due to higher blood pressure, because heart rate responses were not altered during infusion of the alpha-1-adrenoceptor agonist phenylephrine (titrated to an equal increase of systolic blood pressure). In the presence of equal systolic blood pressure and central venous pressure, we found no difference in MSA during phenylephrine and L-NMMA infusion.

CONCLUSIONS

This study demonstrates a highly specific alteration of baroreceptor regulation of heart rate but not muscle sympathetic activity after inhibition of NO synthesis in healthy volunteers. This suggests an important role of NO in reflex-mediated heart rate regulation in humans.

Abbreviations and Acronyms   LBNP = lower body negative pressure   L-NMMA = NG-monomethyl-L-arginine   MSA = muscle sympathetic nerve activity   NO = nitric oxide

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