title: Endothelial function and myogenic reactivity in small mesenteric arteries of hyperlipidemic pregnant rats.
abstract: Supraphysiological increases in serum triglycerides and cholesterol often occur during pregnancy, but their effects on vascular function are poorly understood. Intraperitoneal injection of the nontoxic surfactant poloxamer 407 (P-407) results in sustained elevation of triglycerides and cholesterol. We asked if P-407-induced hyperlipidemia during late pregnancy adversely affects mesenteric resistance artery vasodilator function. On days 13-15 of pregnancy, rats were given a single intraperitoneal injection of P-407, sterile water vehicle, or non-lipid-altering pluronic F-88 (P-88). Four days postinjection, serum triglycerides, cholesterol, free fatty acids, and the lipid peroxidation product malondialdehyde were significantly increased in P-407-treated rats. Mesenteric arteries from P-407-treated rats displayed significant increases in myogenic reactivity (constrictor responses to step increases in intraluminal pressure). The nitric oxide (NO) blocker N(alpha)-methyl-L-arginine increased the myogenic response in control but not in P-407 arteries, normalizing group differences. Endothelial removal increased myogenic reactivity beyond that of prior NO synthase inhibition in controls and potentiated myogenic reactivity in P-407 arteries such that responses again converged. Relaxation responses to the endothelium-dependent vasodilator methacholine did not differ. We conclude that that P-407-induced hyperlipidemia during pregnancy increases myogenic reactivity due to selective attenuation of an NO-mediated vasodilator component of the myogenic response.
authors.affiliation: Magee-Womens Research Institute and Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA.
authors.forename: R J
authors.initials: RJ
authors.lastname: Ramirez
authors.forename: J
authors.initials: J
authors.lastname: Novak
authors.forename: T P
authors.initials: TP
authors.lastname: Johnston
authors.forename: R E
authors.initials: RE
authors.lastname: Gandley
authors.forename: M K
authors.initials: MK
authors.lastname: McLaughlin
authors.forename: C A
authors.initials: CA
authors.lastname: Hubel
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D020567:Fetal Weight / Q000187:drug effects; D006949:Hyperlipidemias / Q000139:chemically induced / Q000503:physiopathology*; D008315:Malondialdehyde / Q000097:blood; D008638:Mesenteric Arteries / Q000187:drug effects / Q000503:physiopathology*; D020442:Poloxamer; D011247:Pregnancy; D011248:Pregnancy Complications / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014280:Triglycerides / Q000097:blood; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology; D014666:Vasomotor System / Q000187:drug effects / Q000503:physiopathology*; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D005230:Fatty Acids, Nonesterified; D014280:Triglycerides; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D020442:Poloxamer; D019323:omega-N-Methylarginine; D008315:Malondialdehyde; D002784:Cholesterol