High Salt Diet-induced pathology in mice

Background: Diet with increased content of salt (High Salt Diet, HSD) is widely used for accelerating some aging-associated pathology – gastritis, renal, neuronal failure, hypertension development in HSD-sensitive strains of mice. HSD-induced hypertension is a relatively fast model of age-related hypertension and is used to study and treat cardiovascular and other age-associated diseases. In 2-3 weeks being kept on HSD (8% NaCl) aged normotensive mice develop at least 15 mmHg systolic blood pressure elevation compared to baseline, providing a model for studying the efficacy of new cardioprotective and anti-age agents.

The dynamics of systolic blood pressure in C57Bl6/j aged (25-month-old) and adult (4-month-old) mice kept on HSD. Mice are placed in plastic holders set on the warming platform for 2-3 min to achieve stress-reducing and the tail temperature of 32-34°C before the testing. Systolic and diastolic blood pressure (BP) were measured. Mean BP and pulse pressure (PP, difference between systolic and diastolic BP) values were then calculated.

Service details: A standard study design for the model of HSD-induced hypertension includes 3 groups of mice (vehicle dosed, treated with reference compound (optional), and tested compound treated group), 10-15 mice per group, 7 days of acclimatization period, 2-3 weeks of HSD to develop hypertension, and 2-4 weeks of testing and post-treatment observation. Terms of treatment and post-treatment observation could vary. Blood pressure is measured in the tail of a mouse using volume pressure recording sensor technology with the CODA (Kent Scientific, USA) mouse/rat tail-cuff system. Mice treatment procedures include invasive (by IV, IP, SC routes), and non-invasive (PO route, and diet incorporated) routes of drug administration. Gross necropsy is performed on all animals at the endpoint. Specific tests, such as hematological, urinary, and blood clinical chemistry analysis, food intake, physiological tests (for example, grip strength test), histopathology, etc. in combination with more definitive toxic or gross pathology endpoints are available on request.