Arterial baroreceptors in the carotid sinus (CBR) and aortic arch (ABR) regions exert important control over heart rate and peripheral vascular responses to changes in arterial pressure. The relative roles of these two baroreflex pathways on control of sympathetic nerve activity during sustained elevation of arterial pressure in man is unknown. We therefore studied the relative contributions of the carotid versus the aortic baroreflexes on the control of muscle sympathetic nerve activity (MSNA) during elevation of arterial pressure in normal human subjects. In eight normal men (group I), we measured MSNA (microneurography) during sustained elevation of arterial pressure produced by intravenous infusion of phenylephrine (PE) alone (combined ABR and CBR activation) versus during PE infusion with superimposed application of sustained external neck pressure (NP). NP was applied during sustained PE infusion to eliminate the increase in transmural carotid sinus pressure and thus remove CBR activation, thereby causing ABR stimulation alone. Mean arterial pressure was measured directly, central venous pressure was held constant during PE infusion, and MSNA was measured as total activity (burst frequency X amplitude) and expressed as units. Infusion of PE (ABR and CBR activation) increased mean arterial pressure from 87.2 +/- 2.8 to 94.9 +/- 2.9 mm Hg (+/- SE, p less than .001). This was accompanied by a decrease in heart rate from 65.8 +/- 3.4 to 56.1 +/- 3.3 beats/min (p less than .001) and a decrease in MSNA from 236.2 +/- 47.5 to 84.5 +/- 19.3 units (p less than .001). During infusion of PE with superimposed NP (ABR activation alone), mean arterial pressure increased further to 101.2 +/- 2.9 mm Hg (p less than .001 versus control or PE alone), and heart rate returned to control levels of 62.9 +/- 2.0 beats/min (p = NS vs control; p less than .01 PE vs PE plus NP), but MSNA remained reduced at 48.6 +/- 9.2 units (p less than .01 vs control; p = NS vs PE alone). Thus, combined activation of ABR and CBR resulted in a 65 +/- 5% attenution of MSNA, while activation of ABR alone resulted in a 73 +/- 7% attenuation of MSNA. In a separate series of experiments in seven subjects (group II) we used sustained external neck suction alone to activate the CBR (leaving the ABR either unchanged or minimally deactivated) and studied the MSNA responses to this CBR activation.(ABSTRACT TRUNCATED AT 400 WORDS)