Attenuated forearm vasodilative response to intra-arterial atrial natriuretic peptide in patients with heart failure.

Abstract

It has been shown that renal responses to atrial natriuretic peptide (ANP) are markedly attenuated in patients with heart failure. This study aimed to determine if vasodilative response to ANP is altered in patients with heart failure. In patients with heart failure (n=7) and age-matched normal subjects (n=7), forearm blood flow was measured using a strain-gauge plethysmograph during intra-arterial infusion of a.human ANP (50, 100, 200, and 400 ng/min) or nitroglycerin (100, 200, 400, and 600 ng/min). Forearm vasodilatation evoked with intra-arterial a-human ANP in patients with heart failure was considerably less (p<0.01) than that in normal subjects. In contrast, nitroglycerin produced comparable forearm vasodilatation in the two groups. Plasma ANP and cyclic guanosine monophosphate (GMP) levels at rest were higher in patients with heart failure than in normal subjects (p<0.05 for both), but the increases in plasma ANP and cyclic GMP in the venous effluents during intra-arterial ANP infusion did not differ between the two groups. These results indicate that the direct vasodilative effect of ANP on forearm vessels was attenuated in patients with heart failure as compared with that in normal subjects. The mechanisms responsible for this alteration are not clear but might involve mechanisms other than down-regulation of the ANP receptors because the increases in venous plasma cyclic GMP caused by intra-arterial ANP were comparable between patients with heart failure and normal subjects. (Circulation 1990;82:147-153) It has been suggested that atrial natriuretic peptide (ANP) may contribute importantly to the control of circulation and water and electrolyte balance.1-3 Previous investigators have shown that plasma ANP is markedly elevated in patients and animals with heart failure,4-8 which suggests that ANP may play a compensatory role in the control of circulation and fluid balance in heart failure. However, it also has been suggested that ANP binding sites may be down-regulated in patients with heart failure.9 Furthermore, a recent study has suggested that there may be an intracellular defect that prevents the mediation of the hormonal signal of ANP into biological action in animals with heart failure.10 The latter results raise the possibility that the attenuated biological effects of ANP may contribute to the pathophysiology of heart failure. Thus, the exact role of ANP in the control of circulation and fluid balance in heart failure is still not known. Previous investigators have examined the renal and hemodynamic effects of intravenous ANP in large doses in patients with heart failure and in normal subjects.8'11-15 These studies have demonstrated that the renal responses to ANP were markedly attenuated in heart failure. Intravenous ANP had no or little effect on diuresis and natriuresis in patients with heart failure,9'11-13 whereas in normal subjects it caused rapid urine and electrolyte excretion.9'6-22 On the other hand, it has been reported that intra-

Structure, Regulation, and Function of Mammalian Membrane Guanylyl Cyclase Receptors, With a Focus on Guanylyl Cyclase-A

“…116 However, the cardiovascular and cGMP responses to exogenous ANP or BNP are markedly attenuated, indicating a downregulation or impaired receptor or postreceptor responsiveness of GC-A (as demonstrated by Hirooka et al 117 and many others). Some studies have suggested that the decreased biological responses to ANP are partly due to an upregulation of NPR-C receptors in peripheral tissues, leading to increased sequestration and degradation of ANP.…”

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

“…Many studies have detailed the central hemodynamic, arterial, renal, and adrenal effects of exogenous [1][2][3][4][5][6][7][8] and endogenous 9 NPs in animal models of HF 1 and in human HF, 2-9 but little is known about the effects of NPs on the capacitance vasculature in this condition. In the present study, we assessed the effects of all 4 currently known human NPs on the forearm vasculature in matched groups of optimally treated cHF patients.…”

“…[2][3][4][5][6][7] Hirooka et al 4 and Nakamura et al 6,17 reported reduced forearm resistance-vessel responses to intra-arterial infusion of ANP and BNP (but not CNP) in HF patients versus healthy controls. Interestingly, in these studies, changes in FBF to BNP and CNP were less than those in ANP (on an equimolar basis) in healthy controls, but approximately equipotent in patients with HF.…”

“…[1][2][3][4][5][6][7] Despite minimal effects on plasma volume and resistance vessel tone, infusion of NPs in patients with HF has consistently been shown to reduce central venous pressure (CVP). 8,9 This raises the possibility that the venodilator effects of NPs may be preserved in HF.…”

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.…”