Uncoupling of the baroreflex by N(N)-cholinergic blockade in dissecting the components of cardiovascular regulation

Systemic administration of adrenergic agonists and nitric oxide donors is used extensively to determine cardiovascular receptor sensitivity. Conclusions regarding receptor sensitivity in the presence of the baroreflex may be misleading. In 8 normal volunteers, we determined the heart rate and blood pressure changes after incremental bolus doses of isoproterenol, phenylephrine, and sodium nitroprusside before and during neuronal nicotinic cholinergic (N(N)-cholinergic) blockade with trimethaphan. Results are given as median (25th/75th percentile). With trimethaphan, the baroreflex slope (as determined by bolus doses of nitroprusside and phenylephrine) decreased from 24 (22/26) to 0.00 (0.00/0.09) ms/mm Hg (P<0.01). The dose of isoproterenol that decreased systolic blood pressure (SBP) 12.5 mm Hg changed from 0.61 (0.51/5.3) to 0.17 (0.12/0.21) microg (P<0.01); the dose required to increase heart rate 12.5 bpm changed from 0.22 (0.17/0.41) to 0.74 (0.33/2.3) microg (P<0.01). The dose of nitroprusside required to decrease SBP 12.5 mm Hg changed from 2.3 (1.3/3.4) to 0.18 (0.14/0.24) microg/kg (P<0.01). The dose of phenylephrine required to increase SBP 12.5 mm Hg changed from 135 (110/200) to 16 (10/30) microg (P<0.01). We conclude that the efferent arc of the baroreflex can be completely interrupted with N(N)-cholinergic blockade. Estimation of adrenoreceptor sensitivity and sensitivity to nitric oxide donors by systemic administration of agonists is severely confounded by baroreflexes. Uncoupling of the baroreflex by N(N)-cholinergic blockade may be a useful method to obtain an integrated measure of adrenergic receptor sensitivity and sensitivity to nitric oxide donors in humans. This approach would permit the comparison of normal and abnormal physiological states without the "noise" of baroreflex buffering.