Evidence for a specific influence of the nitrergic pathway on the peripheral pulse waveform in rabbits

Abstract

The height of the dicrotic notch between the systolic and diastolic peaks of the peripheral pulse wave, expressed as a fraction of the overall amplitude of the wave, is sensitive to nitric oxide (NO) bioactivity. This phenomenon might form the basis of a simple, non-invasive method for determining endothelial function in vivo. We assessed whether the phenomenon is specific to the NO pathway or whether other vasoactive agents have similar effects. The relative height of the dicrotic notch (RHDN) was determined by photoplethysmography in the rabbit ear. It was dose-dependently decreased by acetylcholine, a stimulator of endothelial NO synthesis, and increased by N G -nitro-L-arginine methyl ester (L-NAME), an inhibitor of NO synthesis. There was no effect on RHDN of the α-adrenergic blocker phentolamine or the β-adrenergic blocker propranolol. The cyclo-oxygenase inhibitor indomethacin dose-dependently decreased RHDN but this effect was blocked by L-NAME, suggesting it was mediated by cross-talk with the NO pathway. Changes in RHDN appeared to be independent of heart rate and of the delay between the systolic peak and the notch, but were associated with changes in the slope of the dicrotic limb. Both L-NAME and phentolamine produced multiple diastolic peaks, indicative of wave reflections in the vasculature. These data support the view that changes in RHDN are specific to the NO pathway and provide additional information about the mechanisms involved.

Modelling pulse wave propagation in the rabbit systemic circulation to assess the effects of altered nitric oxide synthesis

“…It has subsequently emerged that such drugs exert their vasodilatory effect by being metabolized to NO within the vasculature. Consistent with this, recent studies of the pulse wave in the human finger (Chowienczyk et al, 1999) and the rabbit auricular (central ear) artery (Klemsdal et al, 1994;Nier et al, 2008;Weinberg et al, 2001) have shown that alteration of the NO pathway also changes the relative height of the dicrotic notch. Substances that stimulate NO production (e.g.…”

“…L-NAME, type II diabetes, hypercholesterolaemia) increase notch height. Vasoactive drugs unrelated to the NO pathway do not appear to have such effects (Morikawa, 1967;Nier et al, 2008).…”

“…Several studies (e.g. Chowienczyk et al, 1999;Klemsdal et al, 1994;Nier et al, 2008;Weinberg et al, 2001) have investigated the possibility that the shape of peripheral pulse waves could be used in clinical practice and laboratory animal experiments to assess endothelial dysfunction. Such dysfunction is primarily characterised by a reduced production of the vasodilator nitric oxide (NO) by the endothelial cells lining blood vessels and is a major risk factor for cardiovascular disease, but there are currently no convenient, non-invasive methods for detecting it.…”

Low-amplitude pulses to the circulation through periodic acceleration induces endothelial-dependent vasodilatation

“…Since the a/b is a function of arterial wave reflection, the lesser increase of the a/b with SNP compared with pG z can be interpreted as follows: 1) the major site of action of SNP was on large-conduit vessels and pG z on smaller resistance vessels; or 2) pG z also stimulated release of prostacyclin, which provided significant additional vasodilatation to cause the lengthening of the time of wave reflection (4). Nier et al (42) showed, in rabbits, that the relative height of the dicrotic notch was dose dependently decreased by the cyclooxygenase Fig. 7.…”

“…This phenomenon is attributed to vasodilatation of the resistance vessels, thereby lengthening the arterial pulse wave reflection time (26). In humans, descent of the dicrotic notch of digital and aortic pulse waves has been observed with nitrate and albuterol administration, as well as with exercise (10,26,29,39,42,46). This finding is mediated through the action of NO, since inhibition of NO synthesis with N G -nitro-L-arginine methyl ester (L-NAME) or N G -monomethyl-L-arginine prevents descent of the dicrotic notch after acetylcholine or albuterol administration in rabbits and humans, respectively (26, 52).…”