Changes in gene expression of serotonin 5HT2A-R and endothelin ETA-R receptors as markers for early aging of rat aorta

Abstract

Age is the major risk factor for cardiovascular disease. However, mechanisms of the effect of aging on the disease development are still unclear. The aim of this study was to investigate the effect of aging on functional activity and expression of endogenous vasoconstrictor receptors in the rat aorta. Methods. The study was performed on mongrel male rats aged 4 and 12 months. Contraction force of fragments isolated from the thoracic aorta i was measured in anisometric mode using the Mulvani method. RNA was isolation from the aorta using the GeneJET^TM kit; cDNA synthesis was measured using the RevertAid^TM H Minus First Strand cDNA Synthesis Kit (Thermo Fisher Scientific, USA); PCR-RT was performed using the qPCRmix-HS kit (Evrogen, Russia) with primers and fluorescent probes (DNA synthesis, Russia) according to manufacturer’s protocols. Results. Early signs of vascular aging included blood vessel sensitization to the vasoconstrictor effect of serotonin (5HT) due to overexpression of
5HT2A-type receptors (194% of the level in blood vessels of 4-month old rats). The aorta sensitivity to norepinephrine, angiotensin II, arginine vasopressin, and endothelin-1 in 12-month old rats remained the same as in younger animals. The level of ETA-type endothelin receptor mRNA was significantly reduced in the aorta of aging rats (55%). Preservation of vascular sensitivity to the vasoconstrictor action of ET1 with a two fold decrease in the expression of the ETA-R gene indirectly indicated an involvement of these receptors not only in maintaining the vascular tone but also in mediating other ET1 effects. Conclusion. Therefore, increases in the functional activity and expression of serotonin 5HT2A-R along with the hypoexpression of endothelin ETA-R are early manifestations of rat aorta aging and can be considered as markers for age-related changes in blood vessels.