Effect of insulin on the venoconstrictive response to norepinephrine in normal human subjects: the influence of sodium status.
Hyperinsulinemia and insulin resistance have been implicated in the pathogenesis of essential hypertension, with alterations in insulin-induced vasodilatation as one possible mechanism. The aims of this study were to assess the local vasodilatory action of insulin on a dorsal hand vein and the influence of sodium status on the insulin effect in healthy human subjects. Distensibility of a superficial hand vein and response to norepinephrine, insulin, and nitroglycerine were measured by the linear variable differential technique. Fourteen healthy subjects were studied after a low (20 mmol) and high (200 mmol) sodium diet for 7 days. All subjects gained weight (P < .005) and had higher central venous pressure (P = .003) on a high sodium intake. Baseline mean arterial pressure, heart rate, and fasting plasma glucose levels were not significantly different between the two diets. High sodium diet, however, resulted in a higher calculated insulin/glucose ratio (P = .029) implying reduced tissue sensitivity to insulin. Baseline plasma norepinephrine was significantly higher on the low (1.29 +/- 0.13 nmol/L) compared with the high sodium diet (0.79 +/- 0.11 nmol/L) (P < .005). The dorsal hand vein was significantly more dilated at the baseline level on a low sodium (2.60 +/- 0.12 mm) than on a high sodium diet (2.20 +/- 0.12 mm) (P = .034). However, the maximal constriction achieved with norepinephrine was not significantly different between the two diets. Only an insulin dose of 0.8 mU/min on a low sodium diet was able to significantly dilate the norepinephrine preconstricted vein (77 +/- 9% of baseline diameter versus ED50) (P = .002).(ABSTRACT TRUNCATED AT 250 WORDS)
Wong
F S
FS
Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Department of Medicine, Toronto, Ontario, Canada.
Miller
J A
JA
Blendis
L M
LM
Logan
A G
AG
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D006225:Hand / Q000098:blood supply; D006439:Hemodynamics / Q000187:drug effects; D006728:Hormones / Q000097:blood; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D005996:Nitroglycerin / Q000494:pharmacology; D009638:Norepinephrine / Q000097:blood / Q000494:pharmacology*; D012016:Reference Values; D012039:Regional Blood Flow / Q000187:drug effects; D012964:Sodium / Q000097:blood* / Q000652:urine; D012982:Sodium, Dietary / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects*; D014882:Water-Electrolyte Balance / Q000502:physiology
D001786:Blood Glucose; D006728:Hormones; D007328:Insulin; D012982:Sodium, Dietary; D012964:Sodium; D005996:Nitroglycerin; D009638:Norepinephrine