Cardiovascular Function

Hypertension

Non-invasive Blood Pressure & Heart Rate
Blood Pressure and Heart Rate with Dietary Challenge

Significantly increased or decreased blood pressure or heart rate in genetically modified or pharmacologically treated mice can identify potential cardiovascular genetic targets or compound indications.  In the Xenogen Phenotyping Platform, systolic blood pressure, heart rate and body weight are measured in mice consuming a regular chow diet.  This assay can also be performed before and after a dietary challenge.  Both high-salt and high-fat dietary challenges have been utilized in conjunction with measurements of blood pressure and heart rate.    

N^G-Monomethyl-L-Arginine Acetate (L-NMMA) Induced Hypertension Model

Nitric oxide (NO) is a critical vasorelaxant involved in the maintenance of blood pressure. It is produced in endothelial cells from arginine. The chemical reaction is facilitated by endothelial nitric oxide synthase (eNOS). L-NMMA is an inhibitor of nitric oxide synthase. Systemic treatment with L-NMMA leads to depletion of NO levels and a significant rise in systolic blood pressure in experimental animals. The potential anti-hypertensive effects of gene knock-outs and pharmacological agents can be assessed in this model of hypertension.

Angiotensin and Aldosterone System

The angiotensin-aldosterone system plays a major role in regulating blood pressure and fluid retention in response to changes in electrolytes (sodium and potassium) and fluid volume. These components are measured in serum and plasma obtained from mice maintained on normal sodium diets. In addition, the levels of electrolytes (sodium, potassium and chloride) are analyzed in the serum and urine of mice. These data in combination help build a comprehensive picture of the physiology of a genetically modified or pharmacologically treated mouse with respect to blood pressure, electrolyte balance and fluid homeostatis.  

Dyslipidemia

Serum Lipid Profile and Cholesterol Distribution

High levels of serum cholesterol, and alterations in how this cholesterol is packaged into VLDL, LDL and HDL, is associated with an increased risk of atherosclerosis and coronary artery disease. In addition, significant changes in the levels of free fatty acids, triglycerides, phospholipid B and blood clotting can also indicate an increased or decreased risk. In the Caliper Phenotyping Platform, serum cholesterol is determined, and its distribution among the different sub-fractions is examined using Lipoprint. The Lipoprint system is based on the covalent linkage of sudan black dye to the cholesterol molecules in the various sub-fractions, which are subsequently separated using polyacrylamide gel electrophoresis and quantitated using densitometry. The levels of free fatty acids, triglycerides, phospholipid B are determined using various calorimetric methods. Serum Lipid profile is assessed on regular low fat rodent chow and after challenge with a high fat diet.

Thrombosis 

Assessment of Blood Coagulation in vivo and in vitro  (aPTT)

Blood coagulation requires coordinated interactions between plasma derived enzymes, co-factors, inhibitors, and blood and vascular cells.  Impairment in clot formation may cause pulmonary embolism, stroke, myocardial infarction, etc. Our thrombosis package assesses various aspects of the blood coagulation process in mice. Thus, the tail bleeding time test is designed to assess clot formation in vivo, while the in vitro blood coagulation analysis evaluates the intrinsic and extrinsic pathways of blood coagulation by measuring prothrombin time (PT) and activated partial thromboplastin time (aPTT). The collagen-induced platelet aggregation test assays the contribution of the platelets in clot formation. In addition, the assessment of the thrombin anti-thrombin complex III (TAT) in mouse plasma defines the rate of thrombin generation and subsequent activation of the coagulation system. This thrombosis package is useful for characterization of both genetic and pharmacological effects on the blood coagulation system.