Endothelin-1 is a very potent vasoconstrictor. The effects of endothelin receptor A (ETA) blockade on major vasoactive systems contributing to blood pressure regulation was evaluated in Ren-2 transgenic rats, in which hypertension is associated with the insertion of murine Ren-2 gene. We found that blood pressure lowering effect of ETA blockade was mediated by the reduced Ca influx through L-type voltage-dependent calcium channels due to missing ETA receptor-dependent vasoconstriction and attenuated angiotensin II-dependent vasoconstriction.
Vaněčková I et al: Endothelin A receptor blocker atrasentan lowers blood pressure by the reduction of nifedipine-sensitive calcium influx in Ren-2 transgenic rats fed a high-salt diet. J Hypertens. 2015, 33(1): 161-9
In cooperation with dr. Lenka Maletínská group from the Institute of Organic Chemistry and Biochemistry ASCR, where lipidized analogs of neuropeptide prolactin releasing peptide (PrRP) were synthesized, we studied the properties of these analogs in vitro (binding to receptors, stability in plasma, etc.) and their effect on food intake in rodents after peripheral administration. We found a very strong binding to the cells expressing PrRP receptor. Peripheral administration of palmitoylated PrRP to fasted mice led to long lasting reduction of food intake, which was associated with an increased neuronal activity in brain areas involved in the regulation of food intake. Long-term administration of analogs in obese mice resulted in decreased food intake, weight loss and normalization of some metabolic parameters. The results clearly showed that lipidized analogues of PrRP could become attractive candidates for the treatment of obesity.
Maletínská L et al: Novel lipidized analogs of prolactin-releasing peptide have prolonged half-lives and exert anti-obesity effects after peripheral administration, International Journal of Obesity. 2015, 39(6): 986-993.
The role of alterations in Ca2+ sensitization (RhoA/Rho kinase pathway) and Ca2+ entry via voltage-gated Ca2+ channels were studied in developing spontaneously hypertension rats. Ca2+ sensitization is attenuated and Ca2+ entry is enhanced from prehypertensive stages. Reduced expression of upstream activators of Rho kinase and lower expression of CPI-17 (endogenous inhibitor of myosin light chain phosphatase) explain changes of Ca2+ sensitization during genetic hypertension development.
Behuliak M et al: Ontogenetic changes in contribution of calcium sensitization and calcium entry to blood pressure maintenance of Wistar-Kyoto and spontaneously hypertensive rats. J Hypertens. 2015; 33(12): 2443-2454.
Enhanced production of reactive oxygen species (ROS) in the brain and/or kidney has been proposed to participate in the pathogenesis of different forms of hypertension. In our studies, we evaluated the production of superoxide radicals by plasma membrane nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase in brain and kidney of hypertensive Dahl salt-sensitive rats and transgenic rats for the murine Ren-2 renin gene. We have found increased ROS production in the kidney of both hypertensive strains, whereas no changes in ROS formation were detected in the brain.