[Regulation of NHE3 by D1 dopamine receptor during development of spontaneously hypertensive rats].
OBJECTIVE
To determine if spontaneous hypertension is secondary to defective interaction among dopamine receptor, G protein, and Na(+)/H(+) exchanger 3 (NHE3).


METHODS
The inhibitory effect of a D(1) dopamine agonist upon NHE3 activity and its impact upon G(s)alpha/NHE3 binding in renal brush border membrane (BBM) of spontaneously hypertensive rats (SHRs) 2 - 3 weeks before and 12 weeks after the establishment of hypertension were examined. In order to avoid the confounding influence of second messenger on D(1) receptor/NHE3 interaction, study was made in BBM devoid of cytoplasmic component.


RESULTS
NHE3 activity increased with age in Wister-Kyoto (WKY) rats but not in SHRS. D1 receptor expression did change with age in both WKY rats and SHRs. The inhibitory effect of a D(1)-like agonist on NHE3 activity increased with age in WKY rats but not in SHRs. In WKY rats, another D(1)-like agonist, fedoldopam, increased G(s)alpha/NHE3 binding to the same extent in 2 week old and adult rats, but decreased the amount of G(s)(alpha)bound to NHE3 in 2 week old SHRs.


CONCLUSIONS
The decrease of inhibitory effect of D(1)-like agonist upon NHE3 activity in SHRs precedes the development of hypertension. Spontaneous hypertension may be caused, in part, by a decreased interaction between G(s)alpha and NHE3 in BBM secondary to D(1)-like receptor function.
Li
X
X
The First Affiliated Hospital, Sun Yat - sen University of Medical Sciences, Guangzhou 510080, China.
Albrecht
F E
FE
Xu
J
J
Robillard
J E
JE
Eisner
G M
GM
Jose
P A
PA
D000375:Aging / Q000502:physiology; D000818:Animals; D001794:Blood Pressure; D018491:Dopamine Agonists / Q000494:pharmacology*; D018818:Fenoldopam / Q000494:pharmacology*; D019204:GTP-Binding Proteins / Q000378:metabolism; D006973:Hypertension / Q000503:physiopathology*; D007668:Kidney / Q000378:metabolism; D008297:Male; D008871:Microvilli / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017447:Receptors, Dopamine D1 / Q000819:agonists / Q000502:physiology*; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism*
D018491:Dopamine Agonists; D017447:Receptors, Dopamine D1; C000613387:Slc9a3 protein, rat; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers; D019204:GTP-Binding Proteins; D018818:Fenoldopam