Why the study?
Does co-infusion of ANP, BNP, or CNP alter arterial vasodilation compared to ANP alone, and does prolonged infusion cause receptor hyporesponsiveness in healthy men?
Does co-infusion of ANP, BNP, or CNP alter arterial vasodilation compared to ANP alone, and does prolonged infusion cause receptor hyporesponsiveness in healthy men?
The study demonstrates rapid desensitization of the guanylyl-cyclase type A receptor to ANP in humans, without evidence for a BNP-specific receptor.
Prolonged ANP infusion induces vasodilation desensitization; confirms human GC-A receptor tachyphylaxis and questions additive benefit of BNP or CNP co-infusion.
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.
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Komarek et al. (2004) studied this question.
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