Effects of chronic vitamin E deficiency and a high polyunsaturated fatty acid diet on rat mesenteric arterial function.

1. Male rats were deprived as weanlings of dietary vitamin E and fed on a high polyunsaturated fatty acid (PUFA) diet for 6 months. Rats fed on a high PUFA or on an untreated diet served as controls. Mesenteric arterial beds were isolated and perfused at a constant flow rate (5 ml min-1) and the function of sympathetic nerves, smooth muscle and endothelium was assessed. 2. Electrical field stimulation (4-32 Hz, 90 V, 1 ms, for 30 s) elicited frequency-dependent vasoconstriction of the mesenteric arterial preparations. Response curves were similar between untreated control and PUFA-fed control groups. Maximum vasoconstrictor responses (at 24 and 32 Hz) were significantly attenuated in rats deprived of vitamin E and on a high PUFA diet compared to the PUFA-fed controls (P < 0.05). 3. Exogenous noradrenaline (NA; 0.15-500 nmol) elicited dose-dependent constriction of the mesenteric arterial beds. Preparations from rats fed on a high PUFA diet elicited significantly smaller responses compared to the control group. There was no significant difference in constrictor responses of PUFA rats deprived of vitamin E compared to the PUFA controls. Vasoconstrictor responses to doses of adenosine 5'-triphosphate (ATP) (5-5000 nmol) were significantly impaired in vitamin E-deficiency with a high PUFA diet compared to a high PUFA diet alone (P < < 0.001). Constrictor responses to potassium chloride (0.15 mmol) were significantly impaired in vitamin E-deficient PUFA rats compared to the PUFA-fed control group (P < 0.05). 4. Vasodilator responses were assessed in preparations in which tone was raised by continuous perfusion with methoxamine (4-25 microM). Mesenteric arterial beds from PUFA-fed rats deprived of vitamin E acquired significantly less tone, 59.8 +/- 4.6 mmHg (n = 7), than PUFA-fed controls 116.9 +/- 7.6 mmHg (n = 7) (P < 0.001) and were refractory to further increases in tone with further additions of methoxamine. Methoxamine-induced tone of PUFA-fed controls was greater than in P that in the untreated controls (83.9 +/- 7.4 mmHg; n = 5) (P < 0.05). Responses to the endothelium-dependent vasodilators acetylcholine (ACh) and ATP were significantly reduced in preparations from rats fed on the vitamin E-deficient high-PUFA diet compared to PUFA controls. Vasodilator responses to ACh were greater in PUFA controls than in untreated controls and this reached statistical significance at 5 nmol ACh. 5. Vasodilator responses to sodium nitroprusside, which acts directly on the vascular smooth muscle, were similar in untreated control and PUFA control groups. Responses were significantly attenuated in vitamin E-deficient PUFA rats compared to the PUFA control group (P < < 0.001). 6. These results indicate that a combination of a high PUFA diet and vitamin E deficiency impairs mesenteric arterial function at the level of the vascular smooth muscle. A high PUFA diet alone attenuates responses to NA and augments endothelium-dependent vasodilation. The detrimental effects of loss of antioxidant activity due to vitamin E-deficiency on vascular function may be exacerbated by a high PUFA diet.