Vascular adrenergic responsiveness is inversely related to tonic activity of sympathetic vasoconstrictor nerves in humans

Abstract

In humans, sympathetic nerve activity (SNA) at rest can vary several-fold among normotensive individuals with similar blood pressures. We recently showed that a balance exists between SNA and cardiac output, which may contribute to the maintenance of normal blood pressures over the range of resting SNA levels. In the present studies, we assessed whether variability in vascular adrenergic responsiveness has a role in this balance. We tested the hypothesis that forearm vascular responses to noradrenaline (NA) and tyramine (TYR) are related to SNA such that individuals with lower resting SNA have greater adrenergic responsiveness, and vice-versa. We measured multifibre muscle SNA (MSNA; microneurography), arterial pressure (brachial catheter) and forearm blood flow (plethysmography) in 19 healthy subjects at baseline and during intrabrachial infusions of NA and TYR. Resting MSNA ranged from 6 to 34 bursts min(-1), and was inversely related to vasoconstrictor responsiveness to both NA (r = 0.61, P = 0.01) and TYR (r = 0.52, P = 0.02), such that subjects with lower resting MSNA were more responsive to NA and TYR. We conclude that interindividual variability in vascular adrenergic responsiveness contributes to the balance of factors that maintain normal blood pressure in individuals with differing levels of sympathetic neural activity. Further understanding of this balance may have important implications for our understanding of the pathophysiology of hypertension.

Figure 1. Average forearm vasoconstrictor responses to noradrenaline and tyramine in all subjects (n =19)

Both noradrenaline (NA) and tyramine (TYR) caused dose-dependent vasoconstriction; the doses used were designed to elicit similar vasoconstrictor responses between the two drugs.

Figure 2. Relationship between nerve activity and percentage change in blood flow with adrenergic agonists

A, linear regression analysis showing direct relationship between resting muscle sympathetic nerve activity (MSNA) and percentage change in forearm blood flow to NA (4 ng (100 ml)⁻¹ min⁻¹), such that individuals with lower resting MSNA tend to have greater vasoconstriction to NA. B, linear regression analysis showing similar relationship between resting MSNA and percentage change in forearm blood flow with intra-arterial TYR (shown for a dose of 6 μg (100 ml)⁻¹ min⁻¹).

Figure 3. Relationship between nerve activity and absolute change in blood flow with adrenergic agonists

A, linear regression analysis showing direct relationship between resting MSNA and absolute change in forearm blood flow to NA (4 ng (100 ml)⁻¹ min⁻¹), such that individuals with lower resting MSNA tend to have greater vasoconstriction to NA. B, linear regression analysis showing similar relationship between resting MSNA and absolute change in forearm blood flow with intra-arterial TYR (shown for a dose of 6 μg (100 ml)⁻¹ min⁻¹).

Figure 4. Vasoconstrictor responses to tyramine as functions of a-v noradrenaline and resting MSNA

Subgroup analysis of individuals with low (n = 5) and high (n = 4) resting MSNA showing vasoconstrictor responses to TYR as a function of the arteriovenous (a–v) difference in NA during each TYR dose. ANOVA showed significant difference between groups (P = 0.02), such that individuals with low resting MSNA had significantly greater vasoconstriction.