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 en dothelium was assessed. 2 Electrical field stimulation (4-32 Hz, 90 V, 1 ms, for 30s) elicited frequency-dependent vasoconstriction of the m esenteric 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 dep rived of vitamin E and on a high PUFA diet compared to the PUFA-fed co ntrols (P < 0.05). 3 Exogenous noradrenaline (NA;0.15 - 500 nmol) elic ited dose-dependent constriction of the mesenteric arterial beds. Prep arations from rats fed on a high PUFA diet elicited significantly smal ler 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 impai red in vitamin E-deficiency with a high PUFA diet compared to a high P UFA diet alone (P < < 0.001). Constrictor responses to potassium chlor ide (0.15 mmol) were significantly impaired in vitamin E-deficient PUF A rats compared to the PUFA-fed control group (P < 0.05). 4 Vasodilato r responses were assessed in preparations in which tone was raised by continuous perfusion with methoxamine (4-25 mu M). 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 o f PUFA-fed controls was greater than in P that in the untreated contro ls (83.9 +/- 7.4 mmHg; n=5) (P < 0.05). Responses to the endothelium-d ependent vasodilators acetylcholine (ACh) and ATP were significantly r educed in preparations from rats fed on the vitamin E-deficient high-P UFA diet compared to PUFA controls. Vasodilator responses to ACh were greater in PUFA controls than in untreated controls and this reached s tatistical significance at 5 nmol ACh. 5 Vasodilator responses to sodi um nitroprusside, which acts directly on the vascular smooth muscle, w ere similar in untreated control and PUFA control groups. Responses we re 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 me senteric arterial function at the level of the vascular smooth muscle. A. high PUFA diet alone attenuates responses to NA and augments endot helium-dependent vasodilatation. The detrimental effects of loss of an tioxidant activity due to vitamin E-deficiency on vascular function ma y be exacerbated by a high PUFA diet.