RT Journal Article
SR Electronic
T1 Effect of dietary lipids on inotropic responses of isolated rat left atrium: attenuation of maximal responses by an unsaturated fat diet.
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 838
OP 845
VO 241
IS 3
A1 L C Wince
A1 L E Hugman
A1 W Y Chen
A1 R K Robbins
A1 G M Brenner
YR 1987
UL http://jpet.aspetjournals.org/content/241/3/838.abstract
AB The effect of varying the dietary fatty acid composition on inotropic responses to various pharmacological agents was investigated in isolated rat left atrium. Pregnant rats were fed either semisynthetic diets supplemented with coconut oil (saturated fatty acids), sunflower oil (unsaturated) or Purina Rodent Chow. Newborns were exposed through the maternal milk and later fed the same diets throughout adulthood. Sunflower oil caused a significant decrease in the maximal response of adult atria to norepinephrine, epinephrine and isoproterenol compared with the other diets. However, no differences in contractile response to norepinephrine were detected at ages 11 and 30 days, indicating a delayed onset of the response changes. We had previously demonstrated defects in the beta adrenoceptor-adenylate cyclase system in homogenates of atria from adult rats fed sunflower oil that may partly explain the attenuated adrenergic response. Additional inotropic studies were performed to further examine the role of this system. There was no change in the maximal contractile response to agents acting through cyclic AMP [cAMP (adenosine 3',5'-cyclic monophosphate)]-independent mechanisms, calcium and phenylephrine. In contrast, maximal responses to forskolin, 3-isobutyl-1-methylxanthine, and N6,2'-O-dibutyryl cAMP, which act via cAMP-dependent mechanisms, were significantly depressed by dietary sunflower oil. No differences were detected in cAMP hydrolysis by phosphodiesterase. These data are consistent with the hypothesis that alterations in adrenergic responsiveness of rat atria after dietary lipid treatment involve functional changes in the adenylate cyclase pathway distal to the enzyme.