1. ATTENTION TO NOVEL OBJECTS IS ENHANCED IN COHEN ROSENTHAL DIABETIC HYPERTENSIVE RATS AFTER TREATMENT WITH TELMISARTAN
Kenneth Hollander MSc, Firas Younis PhD, Zeev Shemer BSc and Talma Rosenthal MD
Department of Physiology and Pharmacology, Sackler Medical School, Tel Aviv University, Israel
Background
Methods
20 CRDH rats were divided into 4 groups; 2 groups received a Sugar Diet (SD) in the presence or absence of Telmisartan, whereas the Control groups were given the same drug treatment in the absence of the Sugar Diet. Systolic and Diastolic Blood Pressure (BP) as well as post-prandrial blood glucose levels were evaluated before and during treatment with Telmisartan as well as body weights recorded on a weekly basis throughout the experiment. The Novel Object Recognition Test (NORT) was evaluated for all 4 groups as well.
Hypertension and Diabetes commonly co-exist, and this dual pathology may promote vascular dementia and cognitive impairment. CRDH is a rat model expressing both hypertension and diabetes. Telmisartan is an ARB with PPARγ partial agonism shown to have hypoglycemic effects.
Aims
The aim of our study was to examine Telmisartan's capability to protect/combat hypertension and diabetes and to observe its concomitant effects on cognitive impairments.
Results
NORT- Amongst the diabetic CRDH rats fed SD, the Telmisartan treated rats spent significantly more time (20.36 ± 2.03s) with the novel object compared to controls (12.74 ± 0.42s), (p<0.05, Student's t-test). Conversely, the opposite pattern was observed for the familiar object whereby the Telmisartan treated rats spent much less time (2.97± s) compared to controls (16.5 ± 9.4s). Similarly, from the perspective of the objects themselves, only the rats who had received Telmisartan were found to have increased levels of attention time with the novel object (20.36 ± 2.03s) compared to the familiar one, (2.97 ± 1.52s) (p<0.005, Student's t-test), whereas no significant difference was found in attendance time to the two objects (novel vs. familiar) for the untreated control rats. These findings were corroborated by the Discrimination Index, wherein Telmisartan-treated SD-fed rats indicated a value of 0.77 ± 0.01 compared to only 0.12 ± 0.3, although this represented only a trend.
Glucose-A decrease in post-prandrial glucose concentrations in blood plasma were detected in diabetic rats (SD) treated with Telmisartan from the baseline compared levels at both mid-experiment (p<0.05. *) and at the end of the experiment (p<0.05, **), (Student's t-test in both cases).
Blood Pressure- Systolic BP in diabetic, left panel and Control, right panel respectively was significantly reduced from baseline to the end of the experiment in all Telmisartan-treated groups (p<0.05, Student's t-test, *). At the end Telmisartan-treated rats were reduced compared to Controls for both diabetics and Controls, (p<0.05, Student's t-test, **). Similar reductions in diastolic BP were also observed in all of the Telmisartan-treated groups.
Conclusions
These preliminary data suggest that treatment with Telmisartan may ameliorate some of the cognitive deficits associated with hypertension and type 2 diabetes in CRDH rats. The data for the Telmisartan-treated diabetic CRDH rats show that instead of attending to familiar objects these rats spent significantly more time directed towards novel objects in their environment. The opposite trend was observed for the diabetic controls which had not received treatment with Telmisartan. The improvement in cognitive function for those rats receiving Telmisartan appears to correlate with reductions in systolic and diastolic blood pressure and post-prandrial plasma glucose concentrations compared to those for which the drug was absent. In addition to the known positive effects of Telmisartan on improving glycemia and hypertension, the current findings support the fact that Telmisartan also improves cognitive deficits associated with these concomitant pathologies