Impaired renal D(1)-like and D(2)-like dopamine receptor interaction in the spontaneously hypertensive rat.
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.
Ladines
C A
CA
Department of Pediatrics, Georgetown University Medical Center, Washington, District of Columbia 20007, USA.
Zeng
C
C
Asico
L D
LD
Sun
X
X
Pocchiari
F
F
Semeraro
C
C
Pisegna
J
J
Wank
S
S
Yamaguchi
I
I
Eisner
G M
GM
Jose
P A
PA
D000818:Animals; D001692:Biological Transport / Q000502:physiology; D002766:Cholecystokinin / Q000008:administration & dosage; D004195:Disease Models, Animal; D004231:Diuresis / Q000187:drug effects; D018491:Dopamine Agonists / Q000008:administration & dosage; D005919:Glomerular Filtration Rate / Q000187:drug effects / Q000502:physiology; D006973:Hypertension / Q000378:metabolism*; D007261:Infusions, Intra-Arterial; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D007677:Kidney Function Tests; D008297:Male; D009284:Naphthols / Q000008:administration & dosage; D009318:Natriuresis / Q000187:drug effects / Q000502:physiology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017447:Receptors, Dopamine D1 / Q000819:agonists / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000819:agonists / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D050637:Receptors, Dopamine D3; D017422:Sequence Analysis, DNA; D012964:Sodium / Q000378:metabolism
D018491:Dopamine Agonists; C493595:Drd3 protein, rat; D009284:Naphthols; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; C105333:Z1046; D002766:Cholecystokinin; D012964:Sodium