Insulin preincubation effects on rat vessel contractile responses: role of the endothelium.
The effect of contractions elicited with ET1 and AVP after preincubating rat aortic and tail artery rings with a hyperinsulinemic dose (3 nM) of insulin were studied. Insulin preincubation (120 min), in the presence of 0.1 mM L-NAME, depressed contraction of aortic rings to 0.01 microM ET1 (132 +/- 6 vs. 161 +/- 9 mg/mm2 in control, n = 25; p < 0.05) and to 1 microM AVP (84 +/- 7 vs. 110 +/- 9 mg/mm2 in control, n = 16; p < 0.05), but did not modify 45Ca influx to the cell. Insulin-induced relaxation was inhibited by indomethacin 10 microM, an antagonist of prostaglandin synthesis, and also by blockade of insulin receptors with 30 microM genistein. A short insulin preincubation (15 min) did not modify ET1 contractions. In rat tail artery, insulin preincubation (120 min) increased the force developed by ET1 (847 +/- 45 vs. 596 +/- 99 mgF/mgW in controls, n = 14) by stimulating TXA2 release and/or actions. In summary, the present results suggest that endothelial factors are involved in both the vasoconstrictor and vasodilator effects of insulin on rat vessels.
Rebolledo
A
A
Departamento de Ciencias Biológicas, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, Argentina. ar@nahuel.biol.unlp.edu.ar
Rinaldi
G J
GJ
Milesi
V
V
Gómez Alvis
A
A
Grassi de Gende
A O
AO
D000818:Animals; D001011:Aorta; D001127:Arginine Vasopressin / Q000494:pharmacology; D004347:Drug Interactions; D019332:Endothelin-1 / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006946:Hyperinsulinism; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors; D013623:Tail / Q000098:blood supply; D014661:Vasoconstriction / Q000187:drug effects*
D019332:Endothelin-1; D004791:Enzyme Inhibitors; D007328:Insulin; D017482:Receptors, Thromboxane; D001127:Arginine Vasopressin; D019001:Nitric Oxide Synthase; D011451:Prostaglandin-Endoperoxide Synthases; D011505:Protein-Tyrosine Kinases