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Vascular Effects of Natriuretic Peptides in Healthy Men

Division of Cardiology, University Hospital, Zurich

Alain Bernheim, MD

Division of Cardiology, University Hospital, Zurich and Division of Cardiology, University Hospital, Basel, Switzerland

Ruth Schindler, RN

Division of Cardiology, University Hospital, Zurich and Division of Cardiology, University Hospital, Basel, Switzerland

Renate Steden, RN

Division of Cardiology, University Hospital, Zurich

Wolfgang Kiowski, MD

Division of Cardiology, University Hospital, Zurich

Hans Peter Brunner-La Rocca, MD

Division of Cardiology, University Hospital, Zurich and Division of Cardiology, University Hospital, Basel, Switzerland

Background: Most effects of atrial (ANP) and B-type natriuretic peptide (BNP) result from stimulation of the guanylyl-cyclase type A receptor. Chronic elevation causes hyporesponsiveness to ANP, whereas BNP effects tend to be preserved, implying an additional pathway of action. We, therefore, investigated the hemodynamic effects of co-infusion of ANP, BNP, and, as a positive control acting on type B receptor, C-type natriuretic peptide (CNP). Furthermore, vascular responses to short and prolonged infusions were compared to investigate rapid hyporesponsiveness of guanylyl-cyclase type A receptor.

Methods: In 11 healthy volunteers, arterial response to continuous intra-arterial infusion of ANP (60 pmol/100 mL forearm tissue volume [FAV]/min) was assessed by venous occlusion plethysmography. Then, co-infusion of a similar dose of ANP, BNP, or CNP was administered in randomized order. Each infusion phase was followed by a washout period. Then, ANP was restarted, followed by co-infusion of one of the natriuretic peptides not yet infused. After a further washout period, ANP was restarted, followed by co-infusion of the natriuretic peptide not yet co-infused. In 6 subjects, infusion time was adjusted to plasma half-lives (5 times), and in the other 5 subjects, infusion time was 5 minutes.

Results: ANP alone caused the expected vasodilation from 2.7 ± 0.3 mL/min/100 mL FAV to 6.0 ± 0.9 mL/min/100 mL FAV (P < .004). This response remained unchanged in the group that received short-term infusions (6.2 ± 0.8 mL/min/100 mL FAV to 6.6 ± 1.1 mL/min/100mL FAV) but was reduced over time in the group receiving longer-term infusions (6.5 ± 1.2 mL/min/100 mL FAV to 4.5 ± 0.7 mL/min/100mL FAV, P < .05; difference between groups P < .05). Co-infusions of ANP, BNP, and CNP caused minor additional vasodilation (mean 0.8 ± 0.2 mL/min/100ml FAV, P < .01), which did not differ between the different co-infused natriuretic peptides.

Conclusion: Our data provide evidence for rapid desensitization of the guanylyl-cyclase type A receptor in humans, but do not support the presence of a BNP-specific receptor.

Key Words: atrial natriuretic peptide • brain natriuretic peptide • vasodilation • guanylate cyclase receptors • down-regulation

Journal of Cardiovascular Pharmacology and Therapeutics, Vol. 9, No. 4, 263-270 (2004)
DOI: 10.1177/107424840400900406


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