Potential for use of pulse wave analysis in determining the interaction between sildenafil and glyceryl trinitrate.
BACKGROUND
The early part of the central aortic pressure pulse, with amplitude (PI - Pd), is generated by left ventricular ejection, while the latter part (or augmented pressure), with amplitude (Ps - Pi), is generated by the reflected wave arriving during systole. The effects of arterial vasodilator agents, especially nitrates, on central aortic systolic blood pressure are grossly underestimated by sphygmomanometric measurements of brachial artery pressure.


OBJECTIVE
The objective of this study was to investigate the potential for use of central arterial pulse wave analysis, obtained noninvasively from the radial pulse, in determining the interaction between sildenafil and the nitric oxide donor drug glyceryl trinitrate (GTN).


METHODS
Central aortic pressure waveforms were generated from noninvasively measured radial artery pressure wave-forms and subjected to pulse wave analysis to determine the interaction between sildenafil and transdermally applied GTN.


RESULTS
Transdermal GTN (2.5, 5.0, and 15 mg per 24-h patches) alone caused no consistent change in sphygmomanometer-determined systolic or diastolic pressures, but there was a consistent, dose-related fall in amplitude of the augmented systolic pressure, (Ps - Pi), of 4.0, 7.0, and 11 mmHg, respectively, with little change in diastolic pressure. The 2.5 mg patch caused a fall of 4.0 mmHg in aortic systolic pressure, while augmentation index (AIx) fell from 20 to 11% and pulse pressure fell 18%. When oral sildenafil (50 mg) was administered after GTN (2.5 mg), aortic systolic pressure fell another 4.0 mmHg. This decrease in systolic pressure caused a fall in AIx to almost 0.0%; pulse pressure fell another 9.0%.


CONCLUSIONS
These modifications in aortic systolic and pulse pressure are due primarily to reduction in wave-reflection amplitude and are not detected by sphygmomanometer-measured brachial artery pressure.
O'Rourke
Michael F
MF
Department of Medicine, St Vincent's Hospital, University of New South Wales, Sydney, Australia. M.ORourke@unsw.edu.au
Nichols
Wilmer W
WW
D000279:Administration, Cutaneous; D001794:Blood Pressure / Q000187:drug effects; D003971:Diastole / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions / Q000502:physiology; D004359:Drug Therapy, Combination; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008875:Middle Aged; D005996:Nitroglycerin / Q000008:administration & dosage*; D010879:Piperazines / Q000008:administration & dosage*; D011673:Pulsatile Flow / Q000187:drug effects*; D011674:Pulse / Q000379:methods*; D011687:Purines; D000068677:Sildenafil Citrate; D019722:Sphygmomanometers; D013450:Sulfones; D013599:Systole / Q000187:drug effects; D013997:Time Factors; D014665:Vasodilator Agents / Q000008:administration & dosage*
D010879:Piperazines; D011687:Purines; D013450:Sulfones; D014665:Vasodilator Agents; D000068677:Sildenafil Citrate; D005996:Nitroglycerin