Blunted coronary vasoreactivity to insulin is an early alteration in hypertension.
Insulin resistance in the heart is not localized to the myocardium, but may also occur in blood vessels. We studied the effects of insulin on coronary vasodilation in hypertension. Coronary vascular resistance was quantitated in 11 nonsmoking men with untreated mild essential hypertension and 9 healthy normotensive men using positron emission tomography and (15)O-labeled water. The measurements were performed at baseline and during adenosine infusion (140 microg x kg(-1) x min(-1)) with or without simultaneous euglycemic physiological (serum insulin approximately 70 mU/l) and supraphysiological (serum insulin approximately 460 mU/l) hyperinsulinemia. Coronary resistance was significantly higher in hypertensive than normotensive subjects at baseline and during adenosine infusion. Physiological hyperinsulinemia decreased hyperemic coronary resistance significantly in both groups. Supraphysiological hyperinsulinemia further decreased the hyperemic coronary resistance in normotensive but not in hypertensive subjects, leading to higher hyperemic coronary resistance in hypertensive than normotensive subjects (27.2 +/- 8.7 vs. 19.2 +/- 4.9 mm Hg x min x g x ml(-1), p < 0.05). However, insulin-stimulated whole body glucose uptake values were similar between the groups during both insulin infusions. In conclusion, insulin-induced coronary vasodilation is blunted in young subjects with mild essential hypertension who are otherwise healthy. Coronary vascular resistance to insulin occurs although no change in peripheral glucose uptake can be detected. While we do not know whether the same results can be extrapolated to female or older subjects, these results indicate a novel defect in the regulation of coronary arteries in the early phase of hypertension.
Sundell
Jan
J
Turku PET Centre, Turku University, Turku, Finland. jan.sundell@utu.fi
Laine
Hanna
H
Luotolahti
Matti
M
Nuutila
Pirjo
P
Kalliokoski
Kari
K
Raitakari
Olli
O
Knuuti
Juhani
J
D000241:Adenosine / Q000008:administration & dosage; D000328:Adult; D001783:Blood Flow Velocity; D001786:Blood Glucose / Q000032:analysis; D001794:Blood Pressure; D003331:Coronary Vessels / Q000187:drug effects* / Q000503:physiopathology*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005947:Glucose / Q000378:metabolism; D015309:Glucose Clamp Technique; D006339:Heart Rate; D006801:Humans; D006973:Hypertension / Q000503:physiopathology*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008297:Male; D009638:Norepinephrine / Q000097:blood; D014055:Tomography, Emission-Computed; D014655:Vascular Resistance / Q000187:drug effects
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D005947:Glucose; D000241:Adenosine; D009638:Norepinephrine