Effects of chronic vitamin E deficiency on vascular function--a study of sympathetic nerves, smooth muscle and endothelium of the mesenteric arterial bed of the rat.
1. Male rats were deprived as weanlings of dietary vitamin E for 2, 4, 6, 10 and 12 months. Mesenteric arterial beds from these rats and from age-matched controls were isolated and perfused with Krebs solution at a constant flow rate (5 ml min-1). The function of perivascular sympathetic nerves, smooth muscle and endothelium was assessed. 2. At 12 months vitamin E deficient rats exhibited the characteristic symptoms of vitamin E deficiency, namely poor coat condition, muscle wasting, kyphoscoliosis and impaired gait. In the isolated mesenteric arterial bed electrical field stimulation (EFS) of perivascular nerves (4-32 Hz, 90 V, 1 ms, for 30 s) elicited frequency-dependent vasoconstrictor responses which were unaffected by vitamin E deficiency except at 12 months, at which age responses were significantly greater than those of the controls at 24 and 32 Hz (P < 0.01). 3. Exogenous noradrenaline (NA; 0.15-500 nmol) elicited dose-dependent vasoconstriction which was similar in vitamin E-deficient and control preparations at all ages. Potassium chloride (0.15 mmol) also produced similar vasoconstrictor responses in vitamin E-deficient and control preparations at each age. 4. Tone of the preparations was raised by continuous perfusion with methoxamine (4-70 microM), producing similar increases in perfusion pressure in vitamin E-deficient and control preparations at each age. Endothelium-dependent dose-dependent vasodilatation to adenosine 5'-triphosphate was significantly impaired in mesenteric arterial beds from 12 month-old vitamin E-deficient rats compared with the controls (P < 0.05). Relaxation to acetylcholine was not significantly different at any age. 5. Endothelium-independent vasodilatation to sodium nitroprusside was similar in vitamin E-deficient rats and age-matched controls. 6. These results suggest that long term (12 months) deprivation of dietary vitamin E may impair endothelial function in mesenteric arteries of the rat. Sympathetic perivascular nerve constrictor function was increased at 12 months. There were no functionally expressed changes in the vascular smooth muscle, which appears to be more resilient to the effects of oxidative stress in vitamin E deficiency.
Ralevic
V
V
Department of Anatomy and Developmental Biology, University College, London.
Milla
P J
PJ
Burnstock
G
G
D000818:Animals; D002908:Chronic Disease; D004558:Electric Stimulation; D004730:Endothelium, Vascular / Q000187:drug effects / Q000294:innervation / Q000503:physiopathology*; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000294:innervation / Q000503:physiopathology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000294:innervation / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D013564:Sympathetic Nervous System / Q000503:physiopathology*; D014666:Vasomotor System / Q000187:drug effects / Q000502:physiology*; D014811:Vitamin E Deficiency / Q000503:physiopathology*