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Role of natriuretic peptides in regulation of conduit artery distensibility

¹Wales Heart Research Institute, Cardiff CF14 4XN, United Kingdom; ²Graduate School of Biomedical Engineering, University of Sydney, New South Wales 2052, Australia; ³Department of Clinical Pharmacology, Addenbrooke's Hospital, Cambridge CB2 2QQ, United Kingdom; and ⁴Medical Data Research Center, St. Vincent Hospital, Providence Health System, Portland, Oregon 97225

Submitted 4 February 2004 ; accepted in final form 4 March 2004

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 (NPR_A)-selective receptor antagonist A71915. Third, A71915 was coinfused with ANP. Fourth, the NPR_C-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 NPR_A receptor. Neither CNP nor cANF altered PWV, suggesting that the NPR_B and NPR_C receptors do not acutely influence distensibility in vivo.

pulse-wave velocity; natriuretic peptide receptors; arterial stiffness

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