N-3 AND N-6 FATTY-ACIDS MODULATE THE INOTROPIC RESPONSE TO CALCIUM INHYPOTHYROID RAT PAPILLARY-MUSCLE

The calcium sensitivity of papillary muscles was enhanced at low [Ca2] in euthyroid rats fed a diet enriched in n-3 fatty acids compared to rats fed diets high in n-6 and saturated (SAT) fatty acids. At the sa me time, the maximum developed tension was 44% lower in animals fed th e n-3 diet compared to those fed the n-6 diet and 62% lower than the r ats fed the SAT diet. In hypothyroid animals fed the n-3 diet, the ino tropic response to added Ca2+ was only 60% of that in euthyroid contro ls and 50 and 65% of euthyroid controls in n-6 and SAT diet-fed animal s, respectively. Although the response was again lower in n-3-fed anim als, the differences among the diet treatments were not as great as th ose seen in euthyroid animals, and there were no apparent diet-depende nt differences in sensitivity to Ca2+ in hypothyroid animals. The pote ncy of the calcium-channel blocker nifedipine was diet-dependent in eu thyroid animals, with the order of decreasing sensitivity being n-3 > n-6 > SAT. Papillary muscles were not as sensitive to nifedipine in hy pothyroid animals, although n-3-fed animals again showed the greatest inhibition of tension development. On the other hand, nitrendipine-bin ding affinity was not different among euthyroid animals fed the three diets, whereas binding-site densities were higher in both euthyroid an d hypothyroid animals fed the n-6 diet. These results suggest that the reduced inotropic response to calcium in the hypothyroid state is not necessarily due entirely to changes in calcium-channel activity, and that contractility is modulated by the type of fatty acid consumed.