Dopamine D3 receptor mRNA and renal response to D3 receptor activation in spontaneously hypertensive rats.
Defective dopamine receptors may be involved in the development of hypertension. Recently, it has been shown that gene expression and function of the renal dopamine D3 receptor is impaired in salt-sensitive Dahl rats, a model of salt-dependent hypertension. Here, the functional response to D3 receptor activation was investigated in spontaneously hypertensive rats (SHR) and their normotensive Wistar-Kyoto rats (WKY). In addition, expression of the D3 receptor gene was studied in both rat strains. In clearance experiments, Ringer solution was infused at baseline in thiopental-anesthetized SHR and WKY (each n = 8), followed by an infusion of R(+)-7-hydroxy-dipropylaminotetralin (DPAT), a specific D3 receptor agonist. DPAT was infused in two consecutive doses of 0.01 and 0.1 microg/min per kg body weight. During the entire experiment mean arterial blood pressure was significantly higher (1.5-fold) in adult SHR when compared to age-matched WKY. In both groups DPAT infusion induced a similar dose-dependent increase in urinary flow rate and sodium excretion by a maximum of 2.3-fold and 3.5-fold, respectively. DPAT also increased the glomerular filtration rate in both SHR and WKY. Reverse transcription-polymerase chain reaction studies of whole kidney samples showed no significant differences between young prehypertensive and adult hypertensive SHR when compared to age-matched normotensive WKY. In summary, pharmacological dopamine D3 receptor activation induces a uniform renal response in SHR and WKY. Together with the similar D3 receptor gene expression in both rat strains, which is independent of age or blood pressure levels, the results do not support the notion that the dopamine D3 receptor system is involved in the pathogenesis of hypertension in the SHR model.
Luippold
Gerd
G
Department of Pharmacology and Toxicology, Faculty of Medicine, University of Tübingen, Tübingen, Germany. gerd.luippold@uni-tuebingen.de
Piesch
Christine
C
Osswald
Hartmut
H
Mühlbauer
Bernd
B
D000818:Animals; D001794:Blood Pressure; D015870:Gene Expression; D005919:Glomerular Filtration Rate; D006977:Hypertension, Renal / Q000378:metabolism / Q000503:physiopathology*; D007668:Kidney / Q000503:physiopathology; D008297:Male; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017448:Receptors, Dopamine D2 / Q000235:genetics* / Q000378:metabolism*; D050637:Receptors, Dopamine D3; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014556:Urine
C493595:Drd3 protein, rat; D012333:RNA, Messenger; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3