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Title: Dietary polyunsaturated fatty acids and vascular and cardiac responses to alpha1-adrenoceptor stimulation
Author: MacLeod, Donald Campbell
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1993
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There is epidemiological evidence that the benefits of dietary polyunsaturated fatty acids (PUFA) derived from fish oil (n-3 PUFA) and plant seed oil (n-6 PUFA) in cardiovascular disease include a reduction in blood pressure (BP). In man, intervention studies have shown that dietary PUFA can affect vascular resistance, an important determinant of BP. Animal experiments have suggested that n-3 PUFA may affect vascular response to α1-adrenoceptor stimulation but differences between species, in experimental diets and duration of feeding make interpretation of results difficult. The aim of this thesis was to use semisynthetic isocalorific experimental diets, representative of what is or could be consumed by man, to investigate the effects of dietary PUFA on cardiovascular responses to α1-adrenoceptor stimulation. Generally, diets derived 40% of total calories from fat. The control diet had a PUFA/saturated fat (P/S) ratio of 0.3. Dietary n-3 PUFA were given as a small daily supplement (0.4% dietary calories) to the control diet. The n-6 PUFA diet had a P/S ratio of 2.0, achieved by substituting 18:2, n-6 for saturated fat. One series of experiments used diets deriving 10&37 of total calories from fat; relatively rich in saturated fat, n-3 PUFA or n-6 PUFA. Diets were fed for eight weeks. There were three experimental preparations: the buffer perfused rat hind-quarters, the isolated rat femoral resistance artery and the isolated rat heart retrogradely perfused with buffer through the aorta. Responses to α1-adrenoceptor stimulation were elicited by noradrenaline in the presence of β- and _2-adrenoceptor antagonists, where appropriate. The effect of the diets on phospholipid (PL) FA composition was monitored in cardiac tissue. In the hind-quarters and resistance artery, dietary n-3 PUFA, but not n-6 PUFA, significantly attenuated response to α1-adrenoceptor stimulation. Dietary PUFA did not affect relaxation of resistance arteries to acetylcholine. In the isolated heart, a 10% fat n-3 PUFA diet, but not an n-6 PUFA diet, significantly attenuated peak left ventricular pressure (LVP) responses to α1-adrenoceptor stimulation. The peak LVP effect of n-3 PUFA was maintained after chemical denervation. At 40% fat, the n-6 PUFA diet significantly attenuated peak LVP responses whereas the n-3 PUFA supplement did not. LVdP.dt^-1, heart rate and coronary flow were not affected by diet. Parenteral flurbiprofen removed the effect of the 40% fat n-6 PUFA diet on peak LVP. Baseline cardiac prostacyclin release decreased 75% with flurbiprofen and was not influenced by diet. In conclusion, dietary PUFA reduced vascular and cardiac responses to α1-adrenoceptor stimulation. Dietary PUFA altered cardiac PL FA composition but no direct relationship could be demonstrated between FA composition and cardiac responses. Dietary PUFA did not affect baseline cardiac prostacyclin release but the attenuatory effect of dietary n-6 PUFA on cardiac peak LVP responses was removed by flurbiprofen. The influence of n-3 PUFA on vascular responses may help to explain BP lowering effects of fish oil in man.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available