Angiotensin blockade prevents salt-induced injury of the renal circulation in spontaneously hypertensive rats.
OBJECTIVE
We hypothesized that renal damage induced by salt overload may be related to increased activity of the renin-angiotensin system. Thus, we examined the renal effects of angiotensin II receptor blockade in spontaneously hypertensive rats (SHR) with salt overload. Two different blockers were used to demonstrate that the effect depends on receptor blockade per se.


METHODS
Male, 8-week-old SHR were divided into 4 groups; the control group was given regular chow, the remaining 3 groups were given chow with 8% salt. In addition, the third group was given candesartan (10 mg/kg/day) and the fourth losartan (30 mg/kg/day). Treatment lasted for 8 weeks.


RESULTS
Compared with controls, mean arterial pressure increased in salt-loaded rats and was not decreased by candesartan or losartan. Indices of renal function including renal blood flow, glomerular filtration rate, and urinary protein excretion were greatly and adversely affected by salt overload, and they were completely restored with either drug.


CONCLUSIONS
These results demonstrated that dietary salt excess adversely affected renal function, hemodynamics and structure. Angiotensin receptor blockade did not affect arterial pressure but prevented other adverse effects of salt overload, indicating that renal damage was not dependent on arterial pressure but, more likely, on another mechanism involving the renin-angiotensin system.
Susic
Dinko
D
Hypertension Research Laboratory, Division of Research, Ochsner Clinic Foundation, New Orleans, LA 70121, USA.
Zhou
Xiaoyan
X
Frohlich
Edward D
ED
D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001011:Aorta / Q000473:pathology; D001562:Benzimidazoles / Q000494:pharmacology / Q000627:therapeutic use; D001713:Biphenyl Compounds; D001835:Body Weight / Q000187:drug effects; D006352:Heart Ventricles / Q000473:pathology; D006439:Hemodynamics / Q000187:drug effects; D006973:Hypertension / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D007668:Kidney / Q000473:pathology; D019808:Losartan / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011918:Rats, Inbred SHR; D012079:Renal Circulation / Q000187:drug effects; D051437:Renal Insufficiency / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D017673:Sodium Chloride, Dietary / Q000009:adverse effects*; D013777:Tetrazoles / Q000494:pharmacology / Q000627:therapeutic use
D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D017673:Sodium Chloride, Dietary; D013777:Tetrazoles; D019808:Losartan; C081643:candesartan