Hypotensive Response to Atrial Natriuretic Peptide Administration Is Enhanced With Age

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Abstract
Background. Plasma levels of atrial natriuretic peptide (ANP) increase with age. To test the hypothesis that the cardiovascular response to ANP is age dependent and to examine the role of the increased levels of ANP in the hypotensive response to orthostatic challenge, we compared the hemodynamic response of young and elderly subjects to ANP infusion and orthostatic challenge. Methods. Blood pressure, heart rate, forearm cutaneous resistance, plasma ANP, and plasma norepinephrine were measured in the supine position and following upright tilt before and after a 60-minute infusion of atrial natriuretic peptide (0.05 μg/kg/min) in 7 young (27 ± 4 years) and 5 elderly (74 ± 4 years) normotensive, healthy subjects. Results. Prior to ANP infusion, the response to upright tilt was similar in both groups. Infusion of ANP produced similar steady state plasma levels of ANP in both groups (young: 435 ± 49 pg/ml; elderly: 429 ± 32 pg/ml). Supine systolic blood pressure decreased by 4 ± 2 mmHg in the young subjects and by 18 ± 8 mmHg in the elderly subjects after infusion (p < .08). In contrast, changes in supine heart rate, forearm cutaneous resistance, and plasma norepinephrine were similar in both groups (Δ heart rate: young +5 ± 3 beats/min, elderly +4 ± 2 beats/min; Δ forearm cutaneous resistance: young−38 ± 9%, elderly−40 ± 6%; Δ norepinephrine: young +55 ± 11%, elderly: +43 ± 13%). ANP infusion abolished the vasoconstrictor response normally associated with orthostatic challenge in both groups, despite a significant release of catecholemines and an enhanced heart rate response. This resulted in significant systolic blood pressure reduction in both young (−7 ± 2 mmHg, p < .05) and elderly subjects (−16 ± 4 mmHg, p < .05). The drop in systolic blood pressure in response to upright tilt and ANP infusion was four times larger in the elderly subjects (change from pre-ANP level: young −8 ± 3 mmHg, elderly −32 ± 5 mmHg, p < .005). Conclusion. Advanced age is associated with a greater hypotensive response to atrial natriuretic peptide infusion.

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