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

Patients with diabetes mellitus (DM) often show arterial pressure (AP) lability associated with cardiovascular autonomic neuropathy. Since the arterial baroreflex tightly regulates AP via sympathetic nerve activity (SNA), we investigated the systematic baroreflex function considering the control theory in DM by an open-loop analysis. We used Zucker Diabetic Fatty (ZDF)-Fatty rats as a type 2 DM model. Under general anesthesia, we isolated the carotid sinuses from systemic circulation, changed intra-carotid sinus pressure (CSP), and recorded SNA and AP responses. We compared the 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 averaged gain in the lower CSP range was markedly reduced in ZDF-Fatty rats (0.03±0.01 vs. 0.87±0.10mmHg/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 study indicated markedly higher AP fall and lower total loop gain of baroreflex in ZDF-Fatty than in ZDF-Lean rats against hypotensive stress, because the efferent arc intersected with the afferent arc in the SNAunresponsive 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.