The Establishment Of Human Dopamine D5 Receptor Transgenic Mice And Its Physiological Study

Dopamine is an endogenour neurotransmitter catecholamine that also serves as a biochemical precursor of norepinephrine and epinephrine. However, dopamine has been characterized as an important modulator of blood pressure, sodium balance through an independent peripheral dopaminergic system. To investigate the role of dopamine D5 receptor in the development of hypertension, we established mutated D5F173L and D5S390G and wild type human dopamine D5 receptor gene transgenic mice. The genotype of transgenic founders and its offsprings were detected by PCR. The expression of dopamine D5 receptor was analyzed by Western Blotting. The non-invasive method, Ultrasonic instrument, was used to analyze the blood pressure and the left ventricular function and structure of transgenic mice and negative littermate controls. The expression of dopamine D5 receptor is higher in kidney of positive transgenic mice with D5F173L, D5S390G, or wild type D5 genes compared with negative controls. The systolic, diastolic and mean arterial blood pressures of D5F173L transgenic mice are higher than D5S390G and wild type D5 gene transgenic mice in each age group from 3 to 6 months old (n=6, P<0.05). The differences of systolic,diastolic and mean arterial blood pressures by age group are not found in each kind of transgenic mice. During diastolic and systolic periods, the volume and diameter of left ventricule are smaller, and the anterior and posterior thickness of left ventricule is thicker in D5F173L transgenic mice than hD5WT transgenic and non-trangenic mice in each age group from 4 to 6 months old. The volume and diameter of ventricule tend to become smaller, and the anterior and posterior thickness of left ventricule tends to become thicker with the age.The results suggest that the dopamine D5 receptor plays an important role in the development of essential hypertension and the regulation of heart structure and function. However, the mechanisms, and the interaction between hypertension and heart structure and function remain to be studied.