Impaired renal D(1)-like and D(2)-like dopamine receptor interaction in the spontaneously hypertensive rat

• Published in: American journal of physiology. Regulatory, integrative and comparative physiology integrative and comparative physiology, 2001-10, Vol.281 (4), p.R1071-R1078
• Main Authors: Ladines, C A, Zeng, C, Asico, L D, Sun, X, Pocchiari, F, Semeraro, C, Pisegna, J, Wank, S, Yamaguchi, I, Eisner, G M, Jose, P A
• Format: Article
• Language: English
• Subjects: Animals; Biological Transport - physiology; Cholecystokinin - administration & dosage; Disease Models, Animal; Diuresis - drug effects; Dopamine Agonists - administration & dosage; Glomerular Filtration Rate - drug effects; Glomerular Filtration Rate - physiology; Hypertension - metabolism; Infusions, Intra-Arterial; Kidney - drug effects; Kidney - metabolism; Kidney Function Tests; Male; Naphthols - administration & dosage; Natriuresis - drug effects; Natriuresis - physiology; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Receptors, Dopamine D1 - agonists; Receptors, Dopamine D1 - metabolism; Receptors, Dopamine D2 - agonists; Receptors, Dopamine D2 - biosynthesis; Receptors, Dopamine D2 - genetics; Receptors, Dopamine D2 - metabolism; Receptors, Dopamine D3; Sequence Analysis, DNA; Sodium - metabolism
• ISSN: 0363-6119

D(1)-like (D(1), D(5)) and D(2)-like (D(2), D(3), D(4)) dopamine receptors interact in the kidney to produce a natriuresis and a diuresis. Disruption of D(1) or D(3) receptors in mice results in hypertension that is caused, in part, by a decreased ability to excrete an acute saline load. We studied D(1)-like and D(2)-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 D(3)> or =D(4)>D(2)>D(5)>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 D(1)-like and D(2)-like receptor interaction is impaired in SHRs. The impaired D(1)-like and D(2)-like receptor interaction in SHRs is not caused by alterations in the coding sequence of the D(3) receptor, the D(2)-like receptor expressed in rat renal tubules that has been shown to be involved in sodium transport. Because the diuretic and natriuretic effects of D(1)-like receptors are, in part, caused by an interaction with D(2)-like receptors, it is possible that the decreased Z-1046 action in SHRs is secondary to the renal D(1)-like receptor dysfunction in this rat strain.