Effects of Exogenous and Endogenous Natriuretic Peptides on Forearm Vascular Function in Chronic Heart Failure

Abstract

Objective-Natriuretic peptides (NPs) reduce central venous pressure in patients with chronic heart failure (cHF) despite attenuation of arterial, renal, and humoral effects. This suggests a preserved venodilator response. This study had 4 aims: to compare the venodilator effects of human NPs in patients with cHF; to assess the contribution of basal ANP and BNP levels to regulation of forearm vascular volume (FVV); to test the hypothesis that venous ANP responsiveness is preserved in cHF; and to assess the involvement of endothelial nitric oxide-synthase (eNOS) in NP-induced vascular effects. Methods and Results-Venous and arterial forearm vascular responses to incremental intra-arterial doses of ANP, Urodilatin, BNP, CNP, or the ANP receptor antagonist A71915 were studied in 53 patients and 11 controls. ANP receptor antagonism reduced FVV by 4.4%Ϯ1.2% (PϽ0.05). The forearm blood flow (FBF) response to ANP was significantly blunted in patients versus controls (PϽ0.01), whereas FVV increased similarly in both groups (maximum 14.7% and 13.4%, both PϽ0.001). The eNOS blockade reduced ANP-induced FBF changes in controls but not in patients (PϽ0.05), whereas similar reductions in FVV changes were seen in groups (both PϽ0.001). Conclusions-In

Effects of human atrial natriuretic peptide on cardiac function and hemodynamics in patients with high plasma BNP levels

“…On the other hand, it has been reported the arterial response to ANP is blunted or disappeared in CHF [27,28]. In the present study, the arterial response to ANP in the high-BNP group was also blunted to compare to the low-BNP group (19% versus 11% reduction of arterial elastance).…”

Novel Snake Venom Ligand Dendroaspis Natriuretic Peptide Is Selective for Natriuretic Peptide Receptor-A in Human Heart

“…39 This suggests that NPR-A may be important in the regulation of vascular smooth muscle tone in a range of vessels. Interestingly, in patients with HF, the efficacy of both endogenous and exogenously infused natriuretic peptide induced vasodilatation is significantly reduced 9,40 when compared with healthy volunteers. In our study, we report that the density of NPR-A in coronary artery is significantly downregulated in IHD patients compared with histologically normal coronary artery.…”

“…6,7 Despite the increase in circulating ANP and BNP, the natriuretic, diuretic, and vasodilatory efficacy of these peptides are dramatically reduced in HF. 8,9 This may reflect increased metabolism or clearance of natriuretic peptides from circulation and/or downregulation of functional natriuretic peptide receptors (NPRs), although other mechanisms, such as desensitization of NPR-A, 10 may also be involved.Three NPR have been identified to date, 2 of which, NPR-A and NPR-B (also known as GC-A and GC-B, respectively), 11 couple to particulate guanylyl cyclase (GC). ANP and BNP bind with high affinity to NPR-A, 12 whereas C-type natriuretic peptide (CNP) binds with high affinity to The third NPR functions predominantly as a nonspecific natriuretic peptide clearance receptor (NPR-C) 13 but has also been shown to activate the pertussis toxin-sensitive protein G i .…”

“…6,7 Despite the increase in circulating ANP and BNP, the natriuretic, diuretic, and vasodilatory efficacy of these peptides are dramatically reduced in HF. 8,9 This may reflect increased metabolism or clearance of natriuretic peptides from circulation and/or downregulation of functional natriuretic peptide receptors (NPRs), although other mechanisms, such as desensitization of NPR-A, 10 may also be involved.…”

Atrial natriuretic peptide and regulation of vascular function in hypertension and heart failure

“…Schmitt et al [51] investigated the venous and arterial FVR responses to incremental doses of ANP, including physiological concentration, in heart failure patients. They confirmed a decreased FVR in response to intra-arterial ANP infusion and observed greater ANP levels in venous effluent in heart failure patients rather than in controls, consistently with NPR-C down-regulation.…”