title: High dietary phosphate intake induces hypertension and augments exercise pressor reflex function in rats.
abstract: An increasing number of studies have linked high dietary phosphate (Pi) intake to hypertension. It is well established that the rise in sympathetic nerve activity (SNA) and blood pressure (BP) during physical exertion is exaggerated in many forms of hypertension, which are primarily mediated by an overactive skeletal muscle exercise pressor reflex (EPR). However, it remains unknown whether high dietary Pi intake potentiates the EPR-mediated SNA and BP response to exercise. Accordingly, we measured renal SNA (RSNA) and mean BP (MBP) in normotensive Sprague-Dawley rats fed a normal Pi diet (0.6%, n = 13) or high Pi diet (1.2%, n = 13) for 3 mo. As previously reported, we found that resting BP was significantly increased by 1.2% Pi diet in both conscious and anesthetized animals. Activation of the EPR by electrically induced hindlimb contraction triggered greater increases in ΔRSNA and ΔMBP in the 1.2% compared with 0.6% Pi group (126 ± 25 vs. 42 ± 9%; 44 ± 5 vs. 14 ± 2 mmHg, respectively, P < 0.01). Activation of the muscle mechanoreflex, a component of the EPR, by passively stretching hindlimb muscle also evoked greater increases in ΔRSNA and ΔMBP in the 1.2% compared with 0.6% Pi group (109 ± 27 vs. 24 ± 7%, 38 ± 7 vs. 8 ± 2 mmHg, respectively, P < 0.01). A similar response was produced by hindlimb intra-arterial capsaicin administration to stimulate the metaboreflex arm of the EPR. Thus, our data demonstrate a novel action of dietary Pi loading in augmenting EPR function through overactivation of both the muscle mechanoreflex and metaboreflex.
authors.affiliation: Department of Health Care Sciences, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas; Cardiology Division, University of Texas Southwestern Medical Center, Dallas, Texas;
authors.forename: Masaki
authors.initials: M
authors.lastname: Mizuno
authors.affiliation: Cardiology Division, University of Texas Southwestern Medical Center, Dallas, Texas;
authors.forename: Jere H
authors.initials: JH
authors.lastname: Mitchell
authors.affiliation: Department of Health Care Sciences, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas;
authors.forename: Scott
authors.initials: S
authors.lastname: Crawford
authors.affiliation: Nephrology Division, University of Texas Southwestern Medical Center, Dallas, Texas; Charles and Jane Pak Center of Mineral Metabolism and Clinical Research, University of Texas Southwestern Medical Center, Dallas, Texas.
authors.forename: Chou-Long
authors.initials: CL
authors.lastname: Huang
authors.affiliation: Mineral Metabolism Division, University of Texas Southwestern Medical Center, Dallas, Texas; and Charles and Jane Pak Center of Mineral Metabolism and Clinical Research, University of Texas Southwestern Medical Center, Dallas, Texas.
authors.forename: Naim
authors.initials: N
authors.lastname: Maalouf
authors.affiliation: Mineral Metabolism Division, University of Texas Southwestern Medical Center, Dallas, Texas; and Charles and Jane Pak Center of Mineral Metabolism and Clinical Research, University of Texas Southwestern Medical Center, Dallas, Texas.
authors.forename: Ming-Chang
authors.initials: MC
authors.lastname: Hu
authors.affiliation: Nephrology Division, University of Texas Southwestern Medical Center, Dallas, Texas; Charles and Jane Pak Center of Mineral Metabolism and Clinical Research, University of Texas Southwestern Medical Center, Dallas, Texas.
authors.forename: Orson W
authors.initials: OW
authors.lastname: Moe
authors.affiliation: Department of Health Care Sciences, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas; Cardiology Division, University of Texas Southwestern Medical Center, Dallas, Texas;
authors.forename: Scott A
authors.initials: SA
authors.lastname: Smith
authors.affiliation: Cardiology Division, University of Texas Southwestern Medical Center, Dallas, Texas; Hypertension Section, University of Texas Southwestern Medical Center, Dallas, Texas; Charles and Jane Pak Center of Mineral Metabolism and Clinical Research, University of Texas Southwestern Medical Center, Dallas, Texas wanpen.vongpatanasin@utsouthwestern.edu.
authors.forename: Wanpen
authors.initials: W
authors.lastname: Vongpatanasin
mesh_terms: D000818:Animals; D017704:Baroreflex / Q000187:drug effects*; D001794:Blood Pressure / Q000187:drug effects*; D002211:Capsaicin / Q000494:pharmacology; D004032:Diet; D006339:Heart Rate / Q000187:drug effects; D006614:Hindlimb / Q000187:drug effects; D006973:Hypertension / Q000139:chemically induced*; D007668:Kidney / Q000187:drug effects / Q000294:innervation; D009119:Muscle Contraction / Q000187:drug effects; D018482:Muscle, Skeletal / Q000187:drug effects; D010710:Phosphates / Q000097:blood / Q000633:toxicity*; D005082:Physical Exertion / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013564:Sympathetic Nervous System / Q000187:drug effects
chemical_list: D010710:Phosphates; D002211:Capsaicin
keywords: Western diet; blood pressure; diet; exercise pressor reflex; hypertension; phosphate; sympathetic nerve activity