Impaired renal D1-like and D2-like dopamine receptor interaction in the spontaneously hypertensive rat
American Journal of Physiology - Regulatory Integrative and Comparative Physiology
Cholecystokinin; D -like receptors 1; D -like receptors 2; Diuresis; Hypertension; Natriuresis
D1-like (D1, D5) and D2-like (D2, D3, D4) dopamine receptors interact in the kidney to produce a natriuresis and a diuresis. Disruption of D1 or D3 receptors in mice results in hypertension that is caused, in part, by a decreased ability to excrete an acute saline load. We studied D1-like and D2-like receptor interaction in anesthetized spontaneously hypertensive rats (SHR) by the intrarenal infusion of Z-1046 (a novel dopamine receptor agonist with rank order potency of D3≥D4>D2≥D5≥D 1). Z-1046 increased glomerular filtration rate (GFR), urine flow, and sodium excretion in normotensive Wistar-Kyoto rats but not in SHRs. The lack of responsiveness to Z-1046 in SHRs was not an epiphenomenon, because intrarenal cholecystokinin infusion increased GFR, urine flow, and sodium excretion to a similar extent in the two rat strains. We conclude that renal D1-like and D2-like receptor interaction is impaired in SHRs. The impaired D1-like and D2-like receptor interaction in SHRs is not caused by alterations in the coding sequence of the D3 receptor, the D2-like receptor expressed in rat renal tubules that has been shown to be involved in sodium transport. Because the diuretic and natriuretic effects of D1-like receptors are, in part, caused by an interaction with D2-like receptors, it is possible that the decreased Z-1046 action in SHRs is secondary to the renal D1-like receptor dysfunction in this rat strain.
Ladines, C., Zeng, C., Asico, L., Xiaoguang, S., Pocchiari, F., Semeraro, C., Pisegna, J., Wank, S., Yamaguchi, I., Eisner, G., & Jose, P. (2001). Impaired renal D1-like and D2-like dopamine receptor interaction in the spontaneously hypertensive rat. American Journal of Physiology - Regulatory Integrative and Comparative Physiology, 281 (4 50-4). http://dx.doi.org/10.1152/ajpregu.2001.281.4.r1071