Role of natriuretic peptides in regulation of conduit artery distensibility

Abstract

Arterial distensibility, assessed by the pulse-wave velocity (PWV), is an independent predictor of cardiovascular risk. We investigated whether natriuretic peptides, acting locally, modify conduit artery distensibility in vivo. All studies were conducted in anesthetized sheep (n = 18) by using a validated ovine hindlimb model. In brief, the PWV was calculated, with the use of the foot-to-foot methodology, from two pressure waveforms recorded simultaneously with a high-fidelity dual pressure-sensing catheter placed in the common iliac artery. Drugs were infused either proximally, via the catheter to perfuse the segment of artery under study, or distally, via the sheath to control for any reflex changes in flow or sympathetic activation. First, the effects of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and c-type natriuretic peptide (CNP) were studied. Second, the role of endogenous ANP was investigated by infusing the natriuretic peptide receptor type A (NPRA)-selective receptor antagonist A71915. Third, A71915 was coinfused with ANP. Fourth, the NPRC-selective agonist cANF was infused. Infusion of CNP or des-[Gln18Ser19Gly20Leu21Gly22]-ANF-(4-23)-NH2 (cANF) had no effect on iliac PWV. However, infusion of ANP, and to a lesser degree BNP, resulted in a reduction in PWV (-9%; P < 0.01 and -6%; P < 0.05, respectively). A71915 increased iliac PWV from 2.97 +/- 0.13 to 3.06 +/- 0.13 m/s; P < 0.01. Coinfusion of A71915 with ANP completely abolished the effects of ANP (P < 0.01). Importantly, ANP-BNP infusion via the sheath did not alter PWV. In conclusion, ANP, and to a lesser extent BNP, modify large artery distensibility via the NPRA receptor. Neither CNP nor cANF altered PWV, suggesting that the NPRB and NPRC receptors do not acutely influence distensibility in vivo.

C-reactive protein and aortic stiffness and wave reflection in middle-aged and elderly men from the community

“…A number of circulating and endothelium-derived factors, including nitric oxide influence large artery stiffness. 23,24 Inflammation is associated with endothelial dysfunction, which may lead to functional stiffening of the large arteries due to reduced nitric oxide bioavailability and increased activity of opposing mediators such as endothelin-1. 25,26 Endothelial dysfunction may lead to a number of changes in the extracellular matrix including smooth muscle cell proliferation and increased synthesis of structural proteins including collagen as well.…”

Large artery stiffness and inflammation

“…We have recently demonstrated that a number of circulating and endothelial-derived factors, including nitric oxide and endothelin-1, influence large artery stiffnessproviding so-called 'functional' regulation of arterial stiffness. [33][34][35] Inflammation is associated with endothelial dysfunction, 11,28 which may lead to functional stiffening of the large arteries due to reduced nitric oxide bioavailability and increased activity of opposing mediators such as endothelin-1. Such a mechanism may also explain why acute vasculitis is potentially associated with reversible stiffening.…”

The influence of mean blood pressure on arterial stiffening and endothelial dysfunction in women with rheumatoid arthritis and systemic lupus erythematosus

“…Several studies demonstrated that inflammation is considered the major cause of endothelial dysfunction and arterial stiffening in both patients' groups. C-reactive protein (CRP) and some of circulating and endothelium-derived factors, including nitric oxide, von Willebrand factor (vWF), excess of adhesive molecules, endothelin-1 may influence the elasticity of large arteries providing so-called "functional" regulation of arterial stiffness (12)(13)(14). Not only active chemical compounds but also disease itself may harm endothelium and induce arterial stiffening.…”