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Diabetes mellitus attenuates the pressure response against hypotensive stress by impairing the sympathetic regulation of the baroreflex afferent arc.
Am J Physiol Heart Circ Physiol. 2019 01 01; 316(1):H35-H44.AJ

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 intracarotid 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 (ΔAP/ΔCSP) 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 unresponsiveness 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.

Authors+Show Affiliations

Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kyushu University , Fukuoka , Japan.Department of Advanced Risk Stratification for Cardiovascular Disease, Center for Disruptive Cardiovascular Medicine, Kyushu University , Fukuoka , Japan.Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kyushu University , Fukuoka , Japan.Department of Cardiovascular Dynamics, National Cerebral and Cardiovascular Center Research Institute , Osaka , Japan.Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kyushu University , Fukuoka , Japan.Department of Anesthesiology and Critical Care Medicine, Graduate School of Medical Sciences, Kyushu University , Fukuoka , Japan.Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kyushu University , Fukuoka , Japan.Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kyushu University , Fukuoka , Japan.Department of Advanced Risk Stratification for Cardiovascular Disease, Center for Disruptive Cardiovascular Medicine, Kyushu University , Fukuoka , Japan.Department of Therapeutic Regulation of Cardiovascular Homeostasis, Center for Disruptive Cardiovascular Medicine, Kyushu University , Fukuoka , Japan.Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kyushu University , Fukuoka , Japan.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30339460

Citation

Kamada, Kazuhiro, et al. "Diabetes Mellitus Attenuates the Pressure Response Against Hypotensive Stress By Impairing the Sympathetic Regulation of the Baroreflex Afferent Arc." American Journal of Physiology. Heart and Circulatory Physiology, vol. 316, no. 1, 2019, pp. H35-H44.
Kamada K, Saku K, Tohyama T, et al. Diabetes mellitus attenuates the pressure response against hypotensive stress by impairing the sympathetic regulation of the baroreflex afferent arc. Am J Physiol Heart Circ Physiol. 2019;316(1):H35-H44.
Kamada, K., Saku, K., Tohyama, T., Kawada, T., Mannoji, H., Abe, K., Nishikawa, T., Sunagawa, G., Kishi, T., Sunagawa, K., & Tsutsui, H. (2019). Diabetes mellitus attenuates the pressure response against hypotensive stress by impairing the sympathetic regulation of the baroreflex afferent arc. American Journal of Physiology. Heart and Circulatory Physiology, 316(1), H35-H44. https://doi.org/10.1152/ajpheart.00515.2018
Kamada K, et al. Diabetes Mellitus Attenuates the Pressure Response Against Hypotensive Stress By Impairing the Sympathetic Regulation of the Baroreflex Afferent Arc. Am J Physiol Heart Circ Physiol. 2019 01 1;316(1):H35-H44. PubMed PMID: 30339460.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Diabetes mellitus attenuates the pressure response against hypotensive stress by impairing the sympathetic regulation of the baroreflex afferent arc. 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, Y1 - 2018/10/19/ PY - 2018/10/20/pubmed PY - 2019/11/15/medline PY - 2018/10/20/entrez KW - arterial pressure KW - arterial pressure lability KW - baroreflex function KW - cardiovascular autonomic neuropathy KW - type 2 diabetes mellitus SP - H35 EP - H44 JF - American journal of physiology. Heart and circulatory physiology JO - Am. J. Physiol. Heart Circ. Physiol. VL - 316 IS - 1 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 intracarotid 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 (ΔAP/ΔCSP) 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 unresponsiveness 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. SN - 1522-1539 UR - https://www.unboundmedicine.com/medline/citation/30339460/Diabetes_mellitus_attenuates_the_pressure_response_against_hypotensive_stress_by_impairing_the_sympathetic_regulation_of_the_baroreflex_afferent_arc_ L2 - http://journals.physiology.org/doi/full/10.1152/ajpheart.00515.2018?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -