Comparison of in vivo effects of nitroglycerin and insulin on the aortic pressure waveform.
BACKGROUND
Individuals whose platelets are resistant to the antiaggregatory effects of insulin in vitro are also resistant to the antiaggregatory effects of nitroglycerin (GTN). We have previously shown that insulin acutely diminishes central wave reflection in large arteries and that this action of insulin is blunted in insulin-resistant subjects. However, as yet, no studies have compared the haemodynamic effects of insulin and GTN on large arterial function in the same group of subjects. The aim of this study was to determine whether resistance to the haemodynamic effects of insulin is a defect specific to insulin or whether individuals resistant to the vascular actions of insulin are also resistant to GTN.


RESULTS
Dose-response characteristics of insulin and GTN on the aortic waveform were determined using applanation tonometry and pulse wave analysis (PWA) in seven healthy men (age 26 +/- 1 year, BMI 25 +/- 2 kg m(-2)). Three doses of sublingual GTN (500 microg for 1, 3 or 5 min) and insulin (0.5, 1 or 2 mU kg(-1) min(-1) for 120 min) were administered on three separate occasions. Both agents dose-dependently decreased central pulse pressure and the augmentation index (AIx) without changing brachial artery blood pressure. We next compared responses to insulin (2 mU kg(-1) min(-1) for 120 min) and sublingual GTN (500 microg for 5 min) in 20 nondiabetic subjects (age 50 +/- 2 year, BMI 21.0-36.3 kg m(-2)). Again, both agents significantly decreased AIx. Although the vascular effects of insulin and GTN vascular were positively correlated [Spearman's r=0.92 (95% confidence interval 0.81-0.97), P<0.0001], the time-course for the action GTN was faster than that of insulin. Brachial systolic blood pressure remained unchanged during the insulin infusion (122 +/- 3 vs. 121 +/- 3 mmHg, 0 vs. 120 min) but aortic systolic blood pressure decreased significantly by 30 min (111 +/- 3 vs. 107 +/- 3 mmHg, 0 vs. 30 min, P<0.01). Similarly, GTN decreased aortic systolic blood pressure from 119 +/- 4 to maximally 112 +/- 3 mmHg (P<0.001) without significantly decreasing systolic blood pressure in the brachial artery.


CONCLUSIONS
The effects of insulin and GTN on large arterial haemodynamics are dose-dependent and significantly correlated. The exact mechanisms and sites of action of insulin and GTN in subjects with insulin resistance remain to be established.
Westerbacka
J
J
Department of Medicine, Division of Diabetes, University of Helsinki, Finland. jukka.westerbacka@helsinki.fi
Tamminen
M
M
Cockcroft
J
J
Yki-Järvinen
H
H
D000286:Administration, Sublingual; D000328:Adult; D001011:Aorta / Q000187:drug effects* / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001795:Blood Pressure Determination / Q000379:methods; D001916:Brachial Artery / Q000502:physiology; D003430:Cross-Sectional Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D007328:Insulin / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D005996:Nitroglycerin / Q000008:administration & dosage / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*
D007004:Hypoglycemic Agents; D007328:Insulin; D014665:Vasodilator Agents; D005996:Nitroglycerin