Protein phosphatase 1b in the solitary tract nucleus is necessary for normal baroreflex function

Amy C. Arnold, Manisha Nautiyal, Debra I. Diz

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Despite positive metabolic effects, genetic deletion of protein phosphatase 1b (PTP1b) results in sympathetically mediated elevations in arterial pressure (AP) in mice. Because several PTP1b-regulated peptides also impair the baroreflex sensitivity (BRS) for control of heart rate (HR), we hypothesized that PTP1b in the solitary tract nucleus (NTS) participates in the maintenance of resting baroreflex function. To test this hypothesis, we performed acute bilateral microinjection of an allosteric PTP1b inhibitor (100 nM/120 nL) in the NTS of urethane/chloralose anesthetized Sprague-Dawley rats and assessed the BRS, responses to cardiac vagal chemosensitive fiber activation, and resting AP and HR before and after the injection. PTP1b inhibition impaired the BRS for bradycardia (n = 6; 0.93 ± 0.14 baseline vs. 0.48 ± 0.04 at 10 minutes vs. 0.49 ± 0.04 millisecond/mm Hg at 60 minutes; P < 0.01), with no significant effect on the BRS for tachycardia (0.30 ± 0.16 baseline vs. 0.24 ± 0.08 at 10 minutes vs. 0.24 ± 0.12 millisecond/mm Hg at 60 minutes). The reduced BRS for bradycardia was associated with a significant decrease in alpha-adrenergic responsiveness to phenylephrine at 60 minutes after PTP1b inhibition. Injection of the PTP1b inhibitor in the NTS elicited transient decreases in AP and HR in these animals. However, there was no effect of the inhibitor on depressor or bradycardic responses elicited by activation of cardiac vagal chemosensitive fibers, which converge with baroreceptor afferents in the NTS. These results suggest that PTP1b within the NTS may be a novel molecular mechanism for preservation of resting baroreflex function and provides further evidence for deleterious cardiovascular effects associated with PTP1b inhibition.

Original languageEnglish (US)
Pages (from-to)472-478
Number of pages7
JournalJournal of Cardiovascular Pharmacology
Volume59
Issue number5
DOIs
StatePublished - May 2012

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

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