Characteristics of the pulse waveform during altered nitric oxide synthesis in the rabbit

Abstract

1 Nitrovasodilators produce characteristic changes in the shape of the peripheral pulse wave. Similar changes might also be caused by alteration of endogenous NO activity, which would allow such activity to be assessed in vivo. 2 We investigated whether manipulation of the NO pathway in¯uences the pulse waveform, and the mechanisms involved. The pulse wave in the ear of normal rabbits was examined by re¯ectance photoplethysmography before and during infusion of vasoactive agents. Pulse wave velocity was assessed by using an additional sensor on the rear foot. 3 A diastolic peak was observed in the ear pulse; its timing was consistent with it being a re¯ection of the systolic peak from the lower body. The height of the dicrotic notch marking the start of this diastolic wave was decreased by acetylcholine or an NO donor, and further decreased by a phosphodiesterase type V inhibitor. The acetylcholine-induced decreases were blocked by inhibiting NO synthesis with N G -nitro-L-arginine methyl ester (L-NAME) but were una ected by the inactive enantiomer D-NAME. 4 These data demonstrate that NO in¯uences the height of the notch in the pulse wave. Heart rate and blood pressure were altered during acetylcholine or L-NAME infusion, but there were no changes in pulse wave amplitude or velocity, or in the timing of the diastolic peak or dicrotic notch. The slope of the pulse wave between the systolic peak and notch changed substantially. These e ects are most convincingly explained by changes in wave re¯ection, not only from the lower body but also from more proximal sites.

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.…”

“…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

“…Weinberg et al (52) have also found a dose-dependent decrease in the relative height of the dicrotic notch or a/b after acetylcholine and SNP, both of which were abolished by L-NAME, and additionally confirmed an NO pathway-mediated effect. Others have found the rise of the a/b in humans after nitroglycerin administration (11,20,22,23,25,38,40,43).…”

“…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).…”

Pulse-Wave Analysis

“…27 Previous studies have shown similar changes in the arterial pressure waveform after NTG, 28,29 but the effect of endothelium-dependent NO dilators has not been reported. Nevertheless, comparable changes in the volume waveform after infusion of ACh into rabbits 30 and of NTG and albuterol into humans 11 have been described. However, unlike Chowienczyk et al 11 and relevant to wider application of the present technique, we included a suitable placebo and showed that the responses to albuterol and NTG are repeatable.…”