2 weeks after arterial injury, we showed that both rat strains developed similar levels of neointimal hyperplasia, but local administration of NO was less effective at inhibiting neointimal hyperplasia in the SHR compared to WRY rats (58% vs. 79%, P < 0.001). Interestingly, local administration of NO did not affect systemic blood pressure in either rat strain. Compared to WRY, the SHR displayed more proliferation in the media and adventitia following balloon injury, as measured by
BrdU incorporation. The SHR also Selleckchem URMC-099 showed more inflammation in the adventitia after injury, as well as more vasa vasorum, than WRY rats. NO treatment reduced the vasa vasorum in the SHR but not WRY rats. Finally, while NO decreased both injury-induced proliferation and inflammation in the SHR, it did not return these parameters to levels seen in WRY rats. We conclude that NO is less effective at inhibiting neointimal hyperplasia in the SHR than WRY rats. This may be due to increased scavenging of NO in the SHR, leading to diminished bioavailability of NO. These data will help to
develop novel NO-based therapies that will be equally effective in both normotensive and hypertensive patient populations. Published by Elsevier Inc.”
“Genetically determined differences in susceptibility to drug-induced sensitization could be related to risk for drug consumption.
Studies were performed DihydrotestosteroneDHT clinical trial to determine whether selective breeding could click here be used to create lines of mice with different magnitudes of locomotor sensitization to methamphetamine (MA). MA sensitization (MASENS) lines were also examined for genetically correlated responses to MA.
Beginning with the F2 cross of C57BL/6J and DBA/2J strains, mice were tested for locomotor sensitization to repeated injections of 1 mg/kg MA and bred based on magnitude of sensitization. Five selected offspring generations were tested. All generations
were also tested for MA consumption, and some were tested for dose-dependent locomotor-stimulant responses to MA, consumption of saccharin, quinine, and potassium chloride as a measure of taste sensitivity, and MA clearance after acute and repeated MA.
Selective breeding resulted in creation of two lines [MA high sensitization (MAHSENS) and MA low sensitization (MALSENS)] that differed in magnitude of MA-induced sensitization. Initially, greater MA consumption in MAHSENS mice reversed over the course of selection so that MALSENS mice consumed more MA. MAHSENS mice exhibited greater sensitivity to the acute stimulant effects of MA, but there were no significant differences between the lines in MA clearance from blood.
Genetic factors influence magnitude of MA-induced locomotor sensitization and some of the genes involved in magnitude of this response also influence MA sensitivity and consumption.