Evidence for biological effects of the hexapeptide novokinin

Abstract

The imbalance of the endogenous renin-angiotensin system is one of the mechanisms involved not only in the hypertension but also in the development of behavioral abnormalities. Activation of angiotensin AT2 and Mas receptors is considered a protective and balancing arm in the renin-angiotensin system, and the synthesis and characterization of selective agonists of these receptors is a promising direction for chemical and pharmacological research.The aim of the present study was to elucidate the effects of intracerebroventricular infusion of the hexapeptide Novokinin, a selective angiotensin AT2 receptor agonist, on anxiety, exploratory behavior, nociception, working and spatial memory in spontaneously hypertensive female rats.The following battery of tests was used: Open Field and Elevated Plus Maze to study exploration and anxiety-like behaviors, object recognition, T-maze for working and spatial memory, and paw pressure for nociception. Novokinin was infused intracerebroventricularly using osmotic minipumps and a stereotaxically implanted brain kit in adult female spontaneous hypertensive rats. All tests were performed twice: at the end of the infusion and three months later. The rats are characterized by hyperactivity, reduced levels of anxiety and impaired spatial memory, which are associated with the strain's inherent impulsive behavior. Novokinin-treated rats showed reduced anxiolysis and hyperactivity as well as increased pain threshold compared to controls. The peptide improves adaptation to the new environment and spatial memory without changes in novel object recognition.In summary, chronic stimulation of brain AT2 receptors by the peptide novokinin improves cognitive behavior and memory and normalizes anxiety-like behavior in spontaneously hypertensive female rats.