Upregulation of the brain renin-angiotensin system in rats with chronic renal failure.
OBJECTIVE
We investigated how the brain renin-angiotensin system is involved in regulation of the sympathetic activity and arterial pressure in rats with chronic renal failure.


METHODS
Systolic arterial pressure, heart rate and diurnal urinary noradrenaline excretion were measured for 12 weeks in spontaneously hypertensive rats (SHR) with or without subtotal nephrectomy. Expression of mRNAs related to the brain renin-angiotensin system was measured using polymerase chain reaction. Effects of a 6-day intracerebroventricular infusion of a type 1 angiotensin II receptor antagonist (candesartan) or bilateral dorsal rhizotomy on these variables were also investigated.


RESULTS
Systolic arterial pressure and urinary excretion of noradrenaline were consistently higher in subtotally nephrectomized SHR than in sham-operated SHR (262 +/- 5 vs. 220 +/- 3 mmHg, P < 0.001; 2.71 +/- 0.22 vs. 1.69 +/-0.19 ng g(-1) body weight day(-1), P < 0.001). Expression of renin, angiotensin-converting enzyme and type 1 angiotensin II receptor mRNAs in the hypothalamus and lower brainstem was greater in subtotally nephrectomized SHR than in sham-operated SHR. Continuous intracerebroventricular infusion of candesartan attenuated hypertension and the increase in urinary noradrenaline excretion in subtotally nephrectomized SHR. Dorsal rhizotomy decreased arterial pressure, urinary excretion of noradrenaline and expression of renin-angiotensin system-related mRNAs in brains of subtotally nephrectomized SHR.


CONCLUSIONS
The brain renin-angiotensin system in subtotally nephrectomized SHR appears to be activated via afferent nerves from the remnant kidney, resulting in sympathetic overactivity and hypertension in this chronic renal failure model.
Nishimura
M
M
Cardiovascular Division, Toujinkai Hospital, Iga, Kyoto, Japan. mnishimura@tea.ocn.ne.jp
Takahashi
H
H
Yoshimura
M
M
D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage; D000818:Animals; D001562:Benzimidazoles / Q000008:administration & dosage; D001713:Biphenyl Compounds; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000187:drug effects / Q000503:physiopathology*; D001933:Brain Stem / Q000187:drug effects / Q000503:physiopathology; D004195:Disease Models, Animal; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D007031:Hypothalamus / Q000187:drug effects / Q000503:physiopathology; D007263:Infusions, Parenteral; D007668:Kidney / Q000503:physiopathology; D007676:Kidney Failure, Chronic / Q000503:physiopathology*; D008297:Male; D009392:Nephrectomy / Q000379:methods; D009638:Norepinephrine / Q000652:urine; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011918:Rats, Inbred SHR; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology*; D019051:Rhizotomy / Q000379:methods; D013777:Tetrazoles / Q000008:administration & dosage; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D012333:RNA, Messenger; D013777:Tetrazoles; C081643:candesartan; D009638:Norepinephrine