Salt induces vascular AT1 receptor overexpression in vitro and in vivo.
The molecular events governing salt-sensitive hypertension are currently unknown. Because the renin-angiotensin system plays a central role in blood pressure regulation, as well as electrolyte balance, it may be closely involved in the phenomenon of salt sensitivity. Therefore, we examined the effect of a high salt diet (8%) on aortic angiotensin type 1 (AT1) receptor expression in Sprague-Dawley rats by means of radioligand binding assays and quantitative polymerase chain reaction. High salt intake caused an increase of AT1 receptor mRNA and AT1 receptor density to approximately 160% compared with control levels. Northern analysis revealed that incubation of vascular smooth muscle cells (VSMCs) with an increased concentration of sodium chloride (by 10 mmol/L) caused a time-dependent elevation of AT1 receptor mRNA levels, with a maximum of 241+/-28% after 24 hours. There was a similar increase in AT1 receptor density in VSMCs in response to sodium chloride, as assessed by radioligand binding assays. The salt-induced AT1 receptor upregulation led to an enhanced functional response of VSMCs on stimulation with angiotensin II, since the angiotensin II-elicited intracellular calcium response was significantly increased in cells preincubated for 24 hours with the high salt concentration. Thus, sodium chloride may directly induce AT1 receptor upregulation in vitro as well as in vivo; this suggests a potential mechanism participating in salt-induced hypertension because the AT1 receptor activation is tightly coupled to blood pressure regulation.
Nickenig
G
G
Klinik III für Innere Medizin, Universität Köln, Germany.
Strehlow
K
K
Roeling
J
J
Zolk
O
O
Knorr
A
A
Böhm
M
M
D000704:Analysis of Variance; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D015152:Blotting, Northern; D002478:Cells, Cultured; D006973:Hypertension / Q000503:physiopathology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000302:isolation & purification; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D011945:Receptors, Angiotensin / Q000032:analysis / Q000235:genetics*; D017673:Sodium Chloride, Dietary / Q000494:pharmacology*; D015854:Up-Regulation
D012333:RNA, Messenger; D011945:Receptors, Angiotensin; D017673:Sodium Chloride, Dietary