Interaction between cholinergic and nitrergic vasodilation: a novel mechanism of blood pressure control

Objective: Cholinergic vasodilation has been thought to play little if any role in the regulation of blood pressure in humans. Autonomic denervation p otentiates the vasoconstriction evoked by nitric oxide synthase inhibition in humans, but the mechanism is unclear. We hypothesized that this may be r elated to loss of neuronal, non-nitric-oxide-dependent vasodilation. Method s: To test this hypothesis, we examined effects of cholinergic blockade on blood pressure, heart rate and peripheral vascular responses to systemic in fusion of the nitric-oxide-dependent vasoconstrictor L-NMMA (0.5 mg/kg/min over 15 min) in eight normal subjects. Results: The L-NMMA-induced increase in mean (+/-S.E.) arterial pressure was roughly three times larger (P=0.00 2) in the presence than in the absence of cholinergic blockade (38 +/-6 vs. 13 +/-2 mmHg). Similarly, the increase in systemic and calf vascular resis tance was more than twofold larger during L-NMMA-atropine. This potentiatio n was specific for nitric-oxide-dependent vasoconstriction, because atropin e did not alter the responses to phenylephrine infusion. Cholinergic blocka de also altered (P=0.004) the heart rate response to nitric oxide synthase inhibition; during L-NMMA alone heart rate decreased by 10 +/-2 beats/min, whereas during L-NMMA-atropine infusion it increased by 14 +/-4 beats/min. Conclusion: Cholinergic mechanisms play an important hitherto unrecognized role in offsetting the hypertension and cardiac sympathetic activation caus ed by nitric oxide synthase inhibition in humans. Decreased parasympathetic activity and impaired nitric oxide synthesis characterize several cardiova scular disease states, as well as normal aging. The conjunction of these tw o defects could trigger sudden death and contribute to the hypertension of the elderly. (C) 2001 Elsevier Science B.V. All rights reserved.