title: High-salt diet enhances vascular reactivity in pregnant rats with normal and reduced uterine perfusion pressure.
abstract: High-salt (HS) diet is often associated with increased vascular resistance and arterial pressure; however, the effects of HS intake on the vascular control mechanisms of arterial pressure during pregnancy are unclear. We investigated whether a HS diet during pregnancy is associated with increases in vascular reactivity. Active stress was measured in aortic strips of virgin and normal pregnant Sprague-Dawley rats and a hypertensive pregnant rat model produced by reduction in uterine perfusion pressure (RUPP), fed either normal-sodium (NS, 1%) or HS diet (8%) for 7 days. In endothelium-intact strips, phenylephrine (Phe) caused a concentration-dependent contraction that was greater in RUPP rats than in normal pregnant or virgin rats and was significantly enhanced in pregnant/HS and RUPP/HS rats compared with pregnant/NS and RUPP/NS rats, respectively. Removal of the endothelium enhanced the Phe-induced stress slightly in virgin rats and significantly in pregnant/NS but not in pregnant/HS, RUPP/NS, or RUPP/HS. In endothelium-intact strips, acetylcholine (ACh) caused a concentration-dependent relaxation that was reduced in RUPP/NS (max, 31%) compared with pregnant/NS rats (max, 75%). ACh relaxation was further reduced in pregnant/HS rats compared with pregnant/NS rats and in RUPP/HS rats compared with RUPP/NS rats. Pretreatment of endothelium-intact strips with N(G)-nitro-L-arginine methyl ester (L-NAME, 10(-4) mol/L), to inhibit NO synthase, or with 1H-[1,2,4]oxadiazolo[4,3]-quinoxalin-1-one (ODQ, 10(-6) mol/L), to inhibit cGMP production in smooth muscle, inhibited ACh-induced relaxation and enhanced Phe-induced contraction in pregnant/NS rats but not in pregnant/HS, RUPP/NS, or RUPP/HS rats. Basal and ACh-induced nitrite/nitrate production from aortic strips showed significant reduction in pregnant/HS rats compared with pregnant/NS rats but not in RUPP/HS rats compared with RUPP/NS rats. Sodium nitroprusside, an exogenous NO donor, caused relaxation of Phe contraction that was similar in virgin or pregnant rats on an NS or HS diet but was significantly reduced in RUPP/HS rats (ED(50) 6x10(-8) mol/L) compared with RUPP/NS rats (ED(50) 6x10(-9) mol/L). Thus, a HS diet in normal pregnant and RUPP rats is associated with increases in vascular reactivity. The enhanced vascular reactivity with the HS diet is possibly related to abnormalities in NO synthesis/release from the endothelium in normal pregnant rats and an additional decrease in the sensitivity of the smooth muscle to relaxation by NO in pregnant rats with reduced uterine perfusion pressure.
authors.affiliation: Department of Physiology and Biophysics and Center for Excellence in Cardiovascular-Renal Research, University of Mississippi Medical Center, Jackson, MI, USA.
authors.forename: L A
authors.initials: LA
authors.lastname: Barron
authors.forename: J B
authors.initials: JB
authors.lastname: Giardina
authors.forename: J P
authors.initials: JP
authors.lastname: Granger
authors.forename: R A
authors.initials: RA
authors.lastname: Khalil
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000502:physiology; D005260:Female; D066298:In Vitro Techniques; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009566:Nitrates / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology; D010069:Oxadiazoles / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011247:Pregnancy; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage*; D014599:Uterus / Q000098:blood supply*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D009566:Nitrates; D009573:Nitrites; D010069:Oxadiazoles; D011810:Quinoxalines; D017673:Sodium Chloride, Dietary; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D009599:Nitroprusside; D010656:Phenylephrine; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester