Angiotensin-(1-12) requires angiotensin converting enzyme and AT 1 receptors for cardiovascular actions within the solitary tract nucleus

Amy C. Arnold, Katsunori Isa, Hossam A. Shaltout, Manisha Nautiyal, Carlos M. Ferrario, Mark C. Chappell, Debra I. Diz

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

The novel peptide, angiotensin (ANG)-(1-12), elicits a systemic pressor response and vasoconstriction. These effects are blocked by ANG converting enzyme (ACE) inhibitors or AT1 receptor antagonists, suggesting a role as an ANG II precursor. However, ANG-(1-12) can serve as a substrate for either ANG II or ANG-(1-7) formation, depending on the local tissue enzymes. Although levels of ANG-(1-12) are higher than ANG I or ANG II in brain, the role and processing of this peptide for autonomic control of heart rate (HR) has yet to be considered. Thus we examined the effects of nucleus tractus solitarii (NTS) microinjection of ANG-(1-12) on baroreflex sensitivity for control of HR, resting arterial pressure (AP) and HR, and indexes of sympathovagal balance in urethane/chloralose anesthetized Sprague-Dawley rats. NTS injection of ANG-(1-12) (144 fmol/120 nl) significantly impaired the evoked baroreflex sensitivity to increases in AP [n = 7; 1.06 ± 0.06 baseline vs. 0.44 ± 0.07 ms/mmHg after ANG-(1-12)], reduced the vagal component of spontaneous baroreflex sensitivity and HR variability, and elicited a transient depressor response (P < 0.05). NTS pretreatment with an AT1 receptor antagonist or ACE inhibitor prevented ANG-(1-12)-mediated autonomic and depressor responses. ANG-(1-12) immunostaining was observed in cells within the NTS of Sprague-Dawley rats, providing a potential intracellular source for the peptide. However, acute NTS injection of an ANG-(1-12) antibody did not alter resting baroreflex sensitivity, AP, or HR in these animals. Collectively, these findings suggest that exogenous ANG-(1-12) is processed to ANG II for cardiovascular actions at AT1 receptors within the NTS. The lack of acute endogenous ANG-(1-12) tone for cardiovascular regulation in Sprague-Dawley rats contrasts with chronic immunoneutralization in hypertensive rats, suggesting that ANG-(1-12) may be activated only under hypertensive conditions.

Original languageEnglish (US)
Pages (from-to)H763-H771
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume299
Issue number3
DOIs
StatePublished - Sep 1 2010

Fingerprint

Solitary Nucleus
Angiotensins
Peptidyl-Dipeptidase A
Baroreflex
Angiotensin II
Heart Rate
Sprague Dawley Rats
Arterial Pressure
Angiotensin-Converting Enzyme Inhibitors
Peptides
Angiotensin I
Chloralose
Injections
Urethane
Microinjections
Vasoconstriction
Cell Nucleus

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Arnold, Amy C. ; Isa, Katsunori ; Shaltout, Hossam A. ; Nautiyal, Manisha ; Ferrario, Carlos M. ; Chappell, Mark C. ; Diz, Debra I. / Angiotensin-(1-12) requires angiotensin converting enzyme and AT 1 receptors for cardiovascular actions within the solitary tract nucleus. In: American Journal of Physiology - Heart and Circulatory Physiology. 2010 ; Vol. 299, No. 3. pp. H763-H771.
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Angiotensin-(1-12) requires angiotensin converting enzyme and AT 1 receptors for cardiovascular actions within the solitary tract nucleus. / Arnold, Amy C.; Isa, Katsunori; Shaltout, Hossam A.; Nautiyal, Manisha; Ferrario, Carlos M.; Chappell, Mark C.; Diz, Debra I.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 299, No. 3, 01.09.2010, p. H763-H771.

Research output: Contribution to journalArticle

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T1 - Angiotensin-(1-12) requires angiotensin converting enzyme and AT 1 receptors for cardiovascular actions within the solitary tract nucleus

AU - Arnold, Amy C.

AU - Isa, Katsunori

AU - Shaltout, Hossam A.

AU - Nautiyal, Manisha

AU - Ferrario, Carlos M.

AU - Chappell, Mark C.

AU - Diz, Debra I.

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N2 - The novel peptide, angiotensin (ANG)-(1-12), elicits a systemic pressor response and vasoconstriction. These effects are blocked by ANG converting enzyme (ACE) inhibitors or AT1 receptor antagonists, suggesting a role as an ANG II precursor. However, ANG-(1-12) can serve as a substrate for either ANG II or ANG-(1-7) formation, depending on the local tissue enzymes. Although levels of ANG-(1-12) are higher than ANG I or ANG II in brain, the role and processing of this peptide for autonomic control of heart rate (HR) has yet to be considered. Thus we examined the effects of nucleus tractus solitarii (NTS) microinjection of ANG-(1-12) on baroreflex sensitivity for control of HR, resting arterial pressure (AP) and HR, and indexes of sympathovagal balance in urethane/chloralose anesthetized Sprague-Dawley rats. NTS injection of ANG-(1-12) (144 fmol/120 nl) significantly impaired the evoked baroreflex sensitivity to increases in AP [n = 7; 1.06 ± 0.06 baseline vs. 0.44 ± 0.07 ms/mmHg after ANG-(1-12)], reduced the vagal component of spontaneous baroreflex sensitivity and HR variability, and elicited a transient depressor response (P < 0.05). NTS pretreatment with an AT1 receptor antagonist or ACE inhibitor prevented ANG-(1-12)-mediated autonomic and depressor responses. ANG-(1-12) immunostaining was observed in cells within the NTS of Sprague-Dawley rats, providing a potential intracellular source for the peptide. However, acute NTS injection of an ANG-(1-12) antibody did not alter resting baroreflex sensitivity, AP, or HR in these animals. Collectively, these findings suggest that exogenous ANG-(1-12) is processed to ANG II for cardiovascular actions at AT1 receptors within the NTS. The lack of acute endogenous ANG-(1-12) tone for cardiovascular regulation in Sprague-Dawley rats contrasts with chronic immunoneutralization in hypertensive rats, suggesting that ANG-(1-12) may be activated only under hypertensive conditions.

AB - The novel peptide, angiotensin (ANG)-(1-12), elicits a systemic pressor response and vasoconstriction. These effects are blocked by ANG converting enzyme (ACE) inhibitors or AT1 receptor antagonists, suggesting a role as an ANG II precursor. However, ANG-(1-12) can serve as a substrate for either ANG II or ANG-(1-7) formation, depending on the local tissue enzymes. Although levels of ANG-(1-12) are higher than ANG I or ANG II in brain, the role and processing of this peptide for autonomic control of heart rate (HR) has yet to be considered. Thus we examined the effects of nucleus tractus solitarii (NTS) microinjection of ANG-(1-12) on baroreflex sensitivity for control of HR, resting arterial pressure (AP) and HR, and indexes of sympathovagal balance in urethane/chloralose anesthetized Sprague-Dawley rats. NTS injection of ANG-(1-12) (144 fmol/120 nl) significantly impaired the evoked baroreflex sensitivity to increases in AP [n = 7; 1.06 ± 0.06 baseline vs. 0.44 ± 0.07 ms/mmHg after ANG-(1-12)], reduced the vagal component of spontaneous baroreflex sensitivity and HR variability, and elicited a transient depressor response (P < 0.05). NTS pretreatment with an AT1 receptor antagonist or ACE inhibitor prevented ANG-(1-12)-mediated autonomic and depressor responses. ANG-(1-12) immunostaining was observed in cells within the NTS of Sprague-Dawley rats, providing a potential intracellular source for the peptide. However, acute NTS injection of an ANG-(1-12) antibody did not alter resting baroreflex sensitivity, AP, or HR in these animals. Collectively, these findings suggest that exogenous ANG-(1-12) is processed to ANG II for cardiovascular actions at AT1 receptors within the NTS. The lack of acute endogenous ANG-(1-12) tone for cardiovascular regulation in Sprague-Dawley rats contrasts with chronic immunoneutralization in hypertensive rats, suggesting that ANG-(1-12) may be activated only under hypertensive conditions.

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