title: Contribution of EDRF and EDHF to restoration of endothelial function following dietary restrictions in hypercholesterolemic rats.
abstract: The mechanisms underlying the impairment of endothelium-mediated vasorelaxation induced by dietary hypercholesterolemia and the mechanisms of restoration of endothelial function following reintroduction of low cholesterol diet were evaluated. Feeding rats with high cholesterol diet induced hypercholesterolemia and high blood pressure. This was associated with reduced vasorelaxation in response to acetylcholine, isoproterenol, and adenosine. At the same time, exaggerated contractile responses to serotonin and phenylephrine were observed. Reintroduction of a normal diet to cholesterol fed rats resulted in significant normalization of blood pressure, serum lipid profile, relaxation and contractile responses. The contributions of endothelial derived relaxing factors (EDRF), endothelial derived contractile factors (EDCFs)/prostanoids, and endothelial derived hyperpoalrising factor (EDHF) to the vasorelaxation in each group of animals were assessed. EDCFs constricting activity was increased in both cholesterol fed groups as compared to the control group. EDRF and EDHF were found to be the primary factors involved in the regulation of endothelium-mediated responsiveness. In control animals, EDRF was responsible for 70-90% of relaxation, depending on the agonist used. In cholesterol fed animals, EDRF was significantly reduced while EDHF was maintained or enhanced showing that EDHF had a significant role in maintaining the endothelial responses. Importantly, the restoration of vasorelaxation following reintroduction of normal diet was mediated not only by improvement of EDRF-dependent relaxation, but also to a significant extent by a further increase in EDHF-mediated relaxation. Taken together, the data showed that EDRF was attenuated during hypercholesterolemia and dietary interventions with low fat content restored these responses. However, EDHF-mediated responses were not reduced by hypercholesterolemia and subsequently improved their function after application of low cholesterol diet. The results implicate EDHF-mediated relaxation is also an important mechanism for restoration of endothelial function upon application of dietary restrictions for reduction of serum cholesterol level.
authors.affiliation: Department of Physiology, V. P. Chest Institute, University of Delhi, Delhi 110007, India.
authors.forename: M Zahid
authors.initials: MZ
authors.lastname: Ashraf
authors.forename: Maram K
authors.initials: MK
authors.lastname: Reddy
authors.forename: M Ejaz
authors.initials: ME
authors.lastname: Hussain
authors.forename: Eugene A
authors.initials: EA
authors.lastname: Podrez
authors.forename: Mohammad
authors.initials: M
authors.lastname: Fahim
mesh_terms: D000818:Animals; D001685:Biological Factors / Q000502:physiology*; D001794:Blood Pressure / Q000187:drug effects; D031204:Caloric Restriction; D004032:Diet; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D045462:Endothelium-Dependent Relaxing Factors / Q000502:physiology*; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006937:Hypercholesterolemia / Q000097:blood / Q000503:physiopathology*; D008055:Lipids / Q000097:blood; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D001685:Biological Factors; D045462:Endothelium-Dependent Relaxing Factors; D008055:Lipids; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; C067410:endothelium-dependent hyperpolarization factor