Angiotensin-converting enzyme inhibition, but not at 1 receptor blockade, in the solitary tract nucleus improves baroreflex sensitivity in anesthetized transgenic hypertensive (mRen2)27 rats

Katsunori Isa, Amy C. Arnold, Brian M. Westwood, Mark C. Chappell, Debra I. Diz

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15 Scopus citations

Abstract

Transgenic hypertensive (mRen2)27 rats overexpress the murine Ren2 gene and have impaired baroreflex sensitivity (BRS) for control of the heart rate. Removal of endogenous angiotensin (Ang)-(1-7) tone using a receptor blocker does not further lower BRS. Therefore, we assessed whether blockade of Ang II with a receptor antagonist or combined reduction in Ang II and restoration of endogenous Ang-(1-7) levels with Ang-converting enzyme (ACE) inhibition will improve BRS in these animals. Bilateral solitary tract nucleus (nTS) microinjections of the AT 1 receptor blocker, candesartan (CAN, 24 pmol in 120 nl, n=9), or a peptidic ACE inhibitor, bradykinin (BK) potentiating nonapeptide (Pyr-Trp-Pro-Arg-Pro-Gln-Ile-Pro-Pro; BPP9α, 9 nmol in 60 nl, n=12), in anesthetized male (mRen2)27 rats (15-25 weeks of age) show that AT 1 receptor blockade had no significant effect on BRS, whereas microinjection of BPP9α improved BRS over 60-120 min. To determine whether Ang-(1-7) or BK contribute to the increase in BRS, separate experiments using the Ang-(1-7) receptor antagonist D-Ala 7-Ang-(1-7) or the BK antagonist HOE-140 showed that only the Ang-(1-7) receptor blocker completely reversed the BRS improvement. Thus, acute AT 1 blockade is unable to reverse the effects of long-term Ang II overexpression on BRS, whereas ACE inhibition restores BRS over this same time frame. As the BPP9α potentiation of BK actions is a rapid phenomenon, the likely mechanism for the observed delayed increase in BRS is through ACE inhibition and elevation of endogenous Ang-(1-7).

Original languageEnglish (US)
Pages (from-to)1257-1262
Number of pages6
JournalHypertension Research
Volume34
Issue number12
DOIs
StatePublished - Dec 2011

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Physiology
  • Cardiology and Cardiovascular Medicine

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