Enhancement of insulin-induced cutaneous vasorelaxation by exercise in rats: A role for nitric oxide and K(Ca2+) channels.
Insulin is a potent vasoactive hormone which induces vasodilatation at physiological concentrations. Aerobic exercise is known to improve insulin vasodilatory activity in humans and experimental animals. Since both insulin and physical training is known to activate K(ATP) and K(Ca2+) channels and increase nitric oxide (NO) synthesis, we hypothesized that insulin and exercise might use a common mechanism in mediating their vascular effect. The present study was carried out to investigate the role of NO, K(ATP) and K(Ca2+) channels in enhancement of insulin-induced cutaneous vasorelaxation by exercise in rats. Male Wistar rats were submitted to exercise training for 8weeks on a treadmill. Cutaneous microvascular response to insulin was recorded from soles skin using a laser Doppler flowmeter. Systemic arterial blood pressure and heart rate were measured using a tail-cuff during assessment of cutaneous blood flow. Subcutaneous injection of insulin induced a dose-dependent increase in skin blood flow in control rats which was significantly higher in exercised animals. Local inhibition of NO synthesis (l-NAME, 10(-4)M) was associated with a marked inhibitory effect on insulin-induced vasodilatation and this inhibition was significantly greater in exercised rats. Likewise, a selective K(Ca2+) channel blocker (iberiotoxin, 10(-9)M) inhibited insulin-induced vasodilatation and this inhibition was significantly exaggerated in exercised animals. Local K(ATP) blockade (glybenclamide, 10(-5)M) showed an identical response in sedentary and exercised animals. Insulin induced a marked vasodilatation in cutaneous microcirculation following aerobic exercise in rats. Both NO and K(Ca2+) channels might be involved in the genesis of this effect.
Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Teheran, Iran.
Samireh
S
Ghafouri
Sohrab
S
Hajizadeh
Ali R
AR
Mani
D000818:Animals; D004305:Dose-Response Relationship, Drug; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology; D007279:Injections, Subcutaneous; D007328:Insulin / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis*; D010805:Physical Conditioning, Animal / Q000502:physiology*; D024681:Potassium Channels, Calcium-Activated / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000187:drug effects; D012867:Skin / Q000098:blood supply / Q000187:drug effects; D013997:Time Factors; D014664:Vasodilation / Q000187:drug effects*
D007004:Hypoglycemic Agents; D007328:Insulin; D024681:Potassium Channels, Calcium-Activated; D009569:Nitric Oxide