Effects of the nitrergic, adrenergic and cyclo-oxygenase pathways on pulse waveform in the rabbit

Bettina A. Nier1, Martin J. Carrier2, Louise S. Harrington2 & Peter D. Weinberg1. 1Department of Bioengineering, Imperial College, London SW7 2AZ, UK, 2Department of Experimental Therapeutics, QMUL, London EC1M 6BQ, UK.

Alteration of NO synthesis changes the shape of the peripheral pulse wave. Increased synthesis decreases the height of the dicrotic notch, relative to the overall height of the wave (“relative height of the dicrotic notch”, RHDN, Fig. 1) , whilst decreased synthesis has the opposite effect. These influences may depend on alteration of vascular wave reflections ( Weinberg et al., 2001 ) . If they were specific, RHDN could provide a simple non-invasive index of NO bioactivity in vivo. Here we used various pharmacological interventions to assess specificity and elucidate mechanisms.

Fig. 1: RHDN (“relative height of the dicrotic notch”) in a typical pulse wave = b/a

Peripheral pulse waves were measured in male New Zealand White rabbits (3-4.8 kg, n=6) by reflectance photoplethysmography after 10 min iv infusion of the drugs. Acetylcholine (ACh; 0.5-4.0 µg/kg/min) produced a significant dose-dependent fall in RHDN (0.14±0.03 vs -0.11±0.06, mean±sem, p=0.042 by Student’s paired t-test) while the NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME; 0.09-0.75 mg/kg/min) produced a dose-dependent rise (0.22±0.03 vs 0.38±0.03, p=0.012), as expected. No large changes were observed with the α-adrenoceptor blocker phentolamine (0.25-2 mg/kg) or the β-adrenoceptor blocker propranolol (0.125-1 mg/kg). The cyclo-oxygenase inhibitor indomethacin (1-8 mg/kg) did produce a clear drop (0.27±0.04 vs 0.16±0.02, p=0.094). However, a subsequent experiment showed that the effect of indomethacin was abolished by L-NAME, and hence was dependent on NO (Fig, 2).

Fig. 2: RHDN after 20 min infusion with indomethacin (Indo, 16 mg/kg) and repeated with L-NAME (1.25 mg/kg/min) the next day (d2). Data show mean±sem. *: p<0.01 to basal, **: p<0.05 to basal d2

Our data confirm the effect of NO on RHDN and show no direct influence of the adrenergic or cyclo-oxygenase pathways. Phentolamine and L-NAME produced multiple pressure peaks after the main systolic peak. This result and other changes observed in the waveform are consistent with the existence and pharmacological modification of wave reflections.

Weinberg, P.D., et al. (2001), Br J Pharmacology 133 : 361-370.

Supported by the BBSRC.