Diabetes mellitus attenuates the pressure response against hypotensive stress by impairing the sympathetic regulation of the baroreflex afferent arc

Kazuhiro Kamada, Keita Saku, Takeshi Tohyama, Toru Kawada, Hiroshi Mannoji, Kiyokazu Abe, Takuya Nishikawa, Genya Sunagawa, Takuya Kishi, Kenji Sunagawa, Hiroyuki Tsutsui

Research output: Contribution to journalArticle

Abstract

Patients with diabetes mellitus (DM) often show arterial pressure (AP) lability associated with cardiovascular autonomic neuropathy. Because the arterial baroreflex tightly regulates AP via sympathetic nerve activity (SNA), we investigated the systematic baroreflex function, considering the control theory in DM by open-loop analysis. We used Zucker diabetic fatty (ZDF) rats as a type 2 DM model. Under general anesthesia, we isolated the carotid sinuses from the systemic circulation, changed intraca-rotid sinus pressure (CSP), and recorded SNA and AP responses. We compared CSP-AP (total loop), CSP-SNA (afferent arc), and SNA-AP (efferent arc) relationships between ZDF lean (n  8) and ZDF fatty rats (n  6). Although the total loop gain of baroreflex (AP/CSP) at the operating point did not differ between the two groups, the average gain in the lower CSP range was markedly reduced in ZDF fatty rats (0.03  0.01 vs. 0.87  0.10 mmHg/ mmHg, P  0.001). The afferent arc showed the same trend as the total loop, with a response threshold of 139.8  1.0 mmHg in ZDF fatty rats. There were no significant differences in the gain of efferent arc between the two groups. Simulation experiments indicated a markedly higher AP fall and lower total loop gain of baroreflex in ZDF fatty rats than in ZDF lean rats against hypotensive stress because the efferent arc intersected with the afferent arc in the SNA unresponsive range. Thus, we concluded that impaired baroreflex sympathetic regulation in the lower AP range attenuates the pressure response against hypotensive stress and may partially contribute to AP lability in DM. NEW & NOTEWORTHY In this study, we investigated the open-loop baroreflex function, considering the control theory in type 2 diabetes mellitus model rats to address the systematic mechanism of arterial pressure (AP) lability in diabetes mellitus. The unresponsive-ness of baroreflex sympathetic regulation in the lower AP range was observed in type 2 diabetic rats. It may attenuate the baroreflex pressure-stabilizing function and induce greater AP fall against hypotensive stress.

Original languageEnglish
Pages (from-to)H35-H44
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume316
Issue number1
DOIs
Publication statusPublished - Jan 1 2019

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Baroreflex
Diabetes Mellitus
Arterial Pressure
Pressure
Type 2 Diabetes Mellitus
Zucker Rats
Carotid Sinus
General Anesthesia

All Science Journal Classification (ASJC) codes

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

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Diabetes mellitus attenuates the pressure response against hypotensive stress by impairing the sympathetic regulation of the baroreflex afferent arc. / Kamada, Kazuhiro; Saku, Keita; Tohyama, Takeshi; Kawada, Toru; Mannoji, Hiroshi; Abe, Kiyokazu; Nishikawa, Takuya; Sunagawa, Genya; Kishi, Takuya; Sunagawa, Kenji; Tsutsui, Hiroyuki.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 316, No. 1, 01.01.2019, p. H35-H44.

Research output: Contribution to journalArticle

Kamada, Kazuhiro ; Saku, Keita ; Tohyama, Takeshi ; Kawada, Toru ; Mannoji, Hiroshi ; Abe, Kiyokazu ; Nishikawa, Takuya ; Sunagawa, Genya ; Kishi, Takuya ; Sunagawa, Kenji ; Tsutsui, Hiroyuki. / Diabetes mellitus attenuates the pressure response against hypotensive stress by impairing the sympathetic regulation of the baroreflex afferent arc. In: American Journal of Physiology - Heart and Circulatory Physiology. 2019 ; Vol. 316, No. 1. pp. H35-H44.
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AU - Kamada, Kazuhiro

AU - Saku, Keita

AU - Tohyama, Takeshi

AU - Kawada, Toru

AU - Mannoji, Hiroshi

AU - Abe, Kiyokazu

AU - Nishikawa, Takuya

AU - Sunagawa, Genya

AU - Kishi, Takuya

AU - Sunagawa, Kenji

AU - Tsutsui, Hiroyuki

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N2 - Patients with diabetes mellitus (DM) often show arterial pressure (AP) lability associated with cardiovascular autonomic neuropathy. Because the arterial baroreflex tightly regulates AP via sympathetic nerve activity (SNA), we investigated the systematic baroreflex function, considering the control theory in DM by open-loop analysis. We used Zucker diabetic fatty (ZDF) rats as a type 2 DM model. Under general anesthesia, we isolated the carotid sinuses from the systemic circulation, changed intraca-rotid sinus pressure (CSP), and recorded SNA and AP responses. We compared CSP-AP (total loop), CSP-SNA (afferent arc), and SNA-AP (efferent arc) relationships between ZDF lean (n  8) and ZDF fatty rats (n  6). Although the total loop gain of baroreflex (AP/CSP) at the operating point did not differ between the two groups, the average gain in the lower CSP range was markedly reduced in ZDF fatty rats (0.03  0.01 vs. 0.87  0.10 mmHg/ mmHg, P  0.001). The afferent arc showed the same trend as the total loop, with a response threshold of 139.8  1.0 mmHg in ZDF fatty rats. There were no significant differences in the gain of efferent arc between the two groups. Simulation experiments indicated a markedly higher AP fall and lower total loop gain of baroreflex in ZDF fatty rats than in ZDF lean rats against hypotensive stress because the efferent arc intersected with the afferent arc in the SNA unresponsive range. Thus, we concluded that impaired baroreflex sympathetic regulation in the lower AP range attenuates the pressure response against hypotensive stress and may partially contribute to AP lability in DM. NEW & NOTEWORTHY In this study, we investigated the open-loop baroreflex function, considering the control theory in type 2 diabetes mellitus model rats to address the systematic mechanism of arterial pressure (AP) lability in diabetes mellitus. The unresponsive-ness of baroreflex sympathetic regulation in the lower AP range was observed in type 2 diabetic rats. It may attenuate the baroreflex pressure-stabilizing function and induce greater AP fall against hypotensive stress.

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