Cerebral Microcirculatory Responses of Insulin‐Resistant Rats are Preserved to Physiological and Pharmacological Stimuli

Abstract

Objective Previously we have shown that insulin resistance impairs the vascular reactivity of the major cerebral arteries of Zucker obese (ZO) rats prior to the occurrence of type-2 diabetes mellitus. However, the functional state of the microcirculation in the cerebral cortex is still being explored. Methods We tested the local cortical blood flow (CoBF) responses of 11–13 week-old ZO (n=31) and control Zucker lean (ZL, n=32) rats to several stimuli measured by laser Doppler flowmetry using a closed cranial window setup. Results The topical application of 1–100μM bradykinin elicited the same degree of CoBF elevation in both ZL and ZO groups. There was no significant difference in the incidence, latency, and amplitude of the N-methyl-D-Aspartate-induced cortical spreading depression-related hyperemia between the ZO and ZL groups. Hypercapnic CoBF response to 5% carbon-dioxide ventilation did not significantly change in the ZO compared to the ZL. Topical bicuculline-induced cortical seizure was accompanied by the same increase of CoBF in both the ZO and ZL at all bicuculline doses. Conclusions CoBF responses of the microcirculation are preserved in the early period of the metabolic syndrome, which creates an opportunity for intervention to prevent and restore the function of the major cerebral vascular beds.

The mitochondrial function of the cerebral vasculature in insulin-resistant Zucker obese rats

“…Our laboratory has shown that mitochondrial-dependent vasodilatory responses of major cerebral arteries are diminished in Zucker obese (ZO) rats (27,28). On the other hand, we have also shown that local cortical microcirculatory responses to pharmacological blood flow stimulators, such as bradykinin, N-methyl-Daspartate (NMDA), bicuculline, and physiologically induced hypercapnia, were not significantly altered in insulin-resistant ZO rats compared with phenotypically normal, Zucker lean (ZL) controls (24).…”

Impact of Metabolic Diseases on Cerebral Circulation: Structural and Functional Consequences

“…Another study using an ex vivo approach showed that MCA relaxation is also diminished in 17-week old obese male Zucker rats (201). However, cerebral microcirculatory responses were preserved as demonstrated by no changes in cortical blood flow in response to topical bradykinin application or carbon dioxide ventilation in 12-week old obese and lean animals suggesting that early preventive strategies can offer vasculoprotection for the microcirculation (127). Interestingly, two groups reported that impairment of endothelium-dependent relaxation occurred despite an increase in eNOS protein suggesting that enzyme activity was dysregulated in obese Zucker rats (223).…”

Synchrotron Radiation Imaging for Advancing Our Understanding of Cardiovascular Function

“…Assessing vascular control of blood flow can involve a variety of methods, such as the use of blood flow-pressure measurements (using thermodilution), 6 velocity measurements using Doppler 7 (assuming constant diameter), or the use of vascular flow probes. 8 Although these techniques certainly have advanced our understanding concerning the control of vascular resistance, they are indirect measurements and have potential inherent sources of error (eg, derived calculations).…”