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.
RCT Entities:
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.