Early vascular abnormalities and de novo nitrate tolerance in diabetes mellitus.
OBJECTIVE
The haemodynamic consequence of altered mechanical wall properties in diabetes can impair the compliance characteristics or pulsatile function of arteries before changes in calibre or peripheral resistance become evident. We studied the sensitivity of pulsatile and steady-state haemodynamic variables in identifying vascular abnormalities and assessing arterial responsiveness to glyceryl trinitrate (GTN) in patients with diabetes, free from clinical complications of the disease.


METHODS
Radial artery pressure waveforms were recorded in 22 patients with diabetes and 22 age- and sex-matched control subjects, using a calibrated tonometer device. A computer-based assessment of the diastolic pressure decay was used to quantify changes in arterial waveform morphology in terms of pulsatile (arterial compliance) and steady-state (peripheral resistance) haemodynamics. Pressure pulse waveforms were recorded before and 3, 6 and 9 min after the administration of 300 micro g of GTN.


RESULTS
Of the pulsatile and steady-state impedance parameters, only small artery compliance was significantly different in patients, 4.7 ml/mmHg (95% CI 3.8-5.8), compared with control subjects 7.1 ml/mmHg (95% CI 5.4-8.7); (p < 0.05). In response to GTN small artery compliance increased, and systemic vascular resistance decreased significantly in control subjects; (p < 0.05) but remained unchanged in patients with diabetes.


CONCLUSIONS
Arterial waveform analysis proved more sensitive in detecting early vascular abnormalities and tracking the haemodynamic effects of GTN in patients with diabetes than changes in total peripheral resistance. The diminished responsiveness of the arterial vasculature to organic nitrates may have therapeutic implications for the treatment of cardiovascular disease in diabetes mellitus.
Department of Therapeutics and Pharmacology, Queen's University, Belfast, Northern Ireland, UK. g.mcveigh@qub.ac.uk
G E
GE
McVeigh
D R
DR
Morgan
P
P
Allen
M
M
Trimble
P
P
Hamilton
L J
LJ
Dixon
B
B
Silke
J R
JR
Hayes
D000328:Adult; D000368:Aged; D001158:Arteries / Q000187:drug effects; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D003925:Diabetic Angiopathies / Q000188:drug therapy* / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D008875:Middle Aged; D005996:Nitroglycerin / Q000627:therapeutic use*; D011673:Pulsatile Flow / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects*; D014665:Vasodilator Agents / Q000627:therapeutic use*
D014665:Vasodilator Agents; D005996:Nitroglycerin