Renal and ocular hemodynamic effects of insulin.
There is evidence that the vasodilator action of insulin is mediated by the release of nitric oxide (NO). We hypothesized that euglycemic hyperinsulinemia might increase renal and ocular blood flow, and that the vasodilator capacity of insulin might be NO-dependent. Euglycemic insulin clamps were performed in 10 healthy subjects. Sixty minutes after the start of insulin administration, an intravenous coinfusion of N-monomethyl-L-arginine (L-NMMA), an inhibitor of NO synthase, or of norepinephrine (NE), an endothelium-independent vasoconstrictor, was started. Renal plasma flow was measured by para-aminohippurate (PAH) clearance method. Ocular hemodynamics were assessed by laser interferometric measurement of fundus pulsations and Doppler sonographic measurement of blood flow velocity in the ophthalmic artery. Renal plasma flow and ocular fundus pulsations were increased by insulin. L-NMMA almost completely abolished the vasodilative effects of insulin, whereas the effects of combined infusion of insulin and NE were approximately the sum of the hemodynamic changes induced by each agent alone. The results show that during euglycemic hyperinsulinemia, renal and ocular blood flow are increased, which may be mediated either by a local vasodilator effect or a systemic increase in flow. The hemodynamic effects of insulin in the kidney and the eye are at least partially dependent on NO synthesis. Because the insulin plasma levels we obtained are in the high physiological range, it may be assumed that insulin plays a role in renal and ocular blood flow regulation.
Schmetterer
L
L
Department of Clinical Pharmacology, Institute of Medical Physics, Vienna University School of Medicine, Austria.
Müller
M
M
Fasching
P
P
Diepolder
C
C
Gallenkamp
A
A
Zanaschka
G
G
Findl
O
O
Strenn
K
K
Mensik
C
C
Tschernko
E
E
Eichler
H G
HG
Wolzt
M
M
D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D004562:Electrocardiography / Q000187:drug effects; D015309:Glucose Clamp Technique; D006439:Hemodynamics / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D006946:Hyperinsulinism; D007262:Infusions, Intravenous; D007328:Insulin / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009569:Nitric Oxide / Q000032:analysis / Q000097:blood; D009638:Norepinephrine / Q000008:administration & dosage / Q000494:pharmacology*; D011674:Pulse; D012039:Regional Blood Flow / Q000187:drug effects; D012079:Renal Circulation / Q000187:drug effects* / Q000502:physiology; D012171:Retinal Vessels / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000502:physiology; D013997:Time Factors; D018615:Ultrasonography, Doppler, Color; D014655:Vascular Resistance / Q000187:drug effects; D019323:omega-N-Methylarginine / Q000008:administration & dosage / Q000494:pharmacology*
D007328:Insulin; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D009638:Norepinephrine