Disorders of the central nervous system cognitive and mnestic functions in genetic arterial hypertension and with the use of beta-blockers of different generations

Abstract

Arterial hypertension is currently one of the most common diseases in the world. A long-term increase in pressure results in changes in the target organs, the healthy functioning of which depends on a stable blood supply (kidneys, eyes, brain), which is primarily caused by damage to small vessels. β-blockers are among the drugs with proven effectiveness in the treatment of hypertension, but their long-term use has different effects on the cognitive sphere, which is determined by the coordination of neurotrophic and neurotransmitter processes in the corresponding brain structures.

Aim. To comparatively analyze the effect of β-blockers from different generations on cognitive and memory functional parameters of the central nervous system in rats with genetically determined hypertension.

Materials and methods. The study used 40 male rats weighing 280–300 g with spontaneous arterial hypertension (SHR) aged 8 months and 10 normotensive control normotensive Wistar–Kyoto rats (WKR) weighing 200–220 g. The animals were divided into 5 experimental groups of 10 rats each. In the experimental study, massometric, instrumental, functional and statistical methods were used with triple measurement of blood pressure by non-invasive Blood Pressure Analysis Systems TM BP-2000 Series II (Visitech Systems, USA). SHR of the 3^rd, 4^th, and 5^th groups were orally administered drugs daily for 30 days, propranolol – 50 mg/kg, carvedilol – 50 mg/kg, and hypertril – 20 mg/kg, respectively. The ability of animals to learn and remember an aversive stimulus was assessed through the conditioned passive avoidance reaction. test Statistical data processing was performed by the package of applied and statistical programs Excel 7.0 (Microsoft Corp., USA) and Statistica (license No. JPZ804I382130ARCN10-J). The significance of differences in study results was determined by pSt ≤ 0.05.

Results. In groups of rats that received β-blockers with different properties (groups 3, 4 and 5), blood pressure was quickly stabilized to target values. A comparative analysis of the cognitive parameters after correction by β-blockers of different generations has shown a significant difference in their effects with proven high effectiveness of hypertril. The drug increased the latency to enter the dark chamber 24 hours after training compared to animals treated with propranolol (group 3) by almost 3-fold, with a 4-fold increase in the percentage of trained animals. The advantages of carvedilol were a 54 % longer latent period and a 2-fold greater number of rats that successfully developed the reflex. Correction with propranolol and carvedilol has proven to be poorly effective in terms of the ability to learn and develop the conditioned-reflex skill with the worst effect of propranolol.

Conclusions. Rats with spontaneous arterial hypertension (SHR) demonstrate a significant decrease in cognitive performance compared to normotensive rats. Drug correction of arterial hypertension with hypertril (a β-blocker of the latest generation with NO-mimetic action) has a highly effective effect on the development of conditioned-reflex skills and the ability to learn that indicates a reduction in cognitive deficits in SHR with essential arterial hypertension.