Developmental change of kidney dopamine receptors in spontaneously hypertensive rats

To elucidate the role of the kidney dopamine system on blood pressure regulation, we investigated the developmental change of kidney dopamine receptors in spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. The autoradiogram of [3H]-SCH23390, a specific DA1 receptor antagonist, showed that DA1 receptors were localized mainly in the rat renal cortex. The radiolabeled receptor assay (RRA) of [3H]-spiperone was performed on 3-, 7-, and 18-week-old SHR using the homogenate of renal cortex. Neither dissociation constant (Kd) nor maximum binding capacity (Bmax) were different between SHR and WKY rats at the age of 3 and 7 weeks. Nevertheless, Kd and Bmax were significantly low in 18-week-old SHR. The systolic blood pressure of 7-, and 18-week-old SHR was significantly higher than that of age matched WKY rats. The urinary dopamine excretion in 16-week-old SHR was significantly higher than that in age-matched WKY rats, although urine volume and urinary sodium excretion were the same as those in the control in both sodium-loaded and -restricted state. In summary, although renal dopamine production was enhanced in SHR in the hypertensive state, dopamine was found not to contribute to natriuresis since the number of dopamine receptors was reduced in these rats. We also found that enhanced dopamine production in response to a salt load was lacking in these rats. These two pathological phenomena noted in the renal dopamine system play a role in the progression of hypertension in SHR.