Insulin improves the endothelium-independent relaxation and the contractile response in aorta from hypertensive diabetic rats.
We investigated the effect of insulin on basal tone and contractile response in isolated aorta from hypertensive streptozotocin-induced diabetic rats (DR) and the role of endothelium in this response. The effect of insulin was tested in rings of control rats (CR) and DR in different protocols: in basal tone, in the plateau of norepinephrine (NE) or KCl contracted rings and in the response to NE or KCl preincubated with insulin. The role of nitric oxide (NO) on insulin response was investigated in rings treated with L-NAME. We found in DR: a) An endothelium independent-vasorelaxant effect of insulin on basal tone; b) A decreased response to NE (without differences in the sensibility) and to KCl (20 mmol/l) and an improvement of this hyporeactivity by insulin pre-treatment, and c) A potentiated vasorelaxant response of insulin dependent of increased vascular tone. Furthermore, an additional action of insulin on endothelial response through NO-release was observed in precontracted vessels from CR, not observed in DR. Our results support that insulin plays a role in regulation of arterial basal tone from DR by a direct effect on smooth muscle vascular cells exposed to high blood pressure. The vasorelaxant effect of insulin dependent of endothelium is blunted in DR by a reduced endothelial NO production. Our work also suggest that insulin could improve the endothelial function in vessels with increased tone in absence of diabetes.
Alonso
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C
Universidad Nacional de Tucuman, INSIBIO-CONICET Departamento Biomédico Orientacion Fisiologia, Facultad de Medicina Balcarce 32, (4000) San Miguel de Tucuman, Argentina.
Proto
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M
Coviello
A
A
Peral de Bruno
M
M
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000503:physiopathology; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000473:pathology / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D006973:Hypertension / Q000150:complications / Q000473:pathology / Q000503:physiopathology*; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology* / Q000502:physiology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000503:physiopathology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
D007328:Insulin; D009569:Nitric Oxide; D011189:Potassium Chloride; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine