Role of angiotensin in renal sympathetic activation in cirrhotic rats.
Central nervous system (CNS) renin-angiotensin activity influences the basal level of renal sympathetic nerve activity (RSNA) and its reflex regulation. The effect of type 1 angiotensin II (ANG II)-receptor antagonist treatment (losartan) on cardiac baroreflex regulation of RSNA and renal sodium handling was examined in rats with cirrhosis due to common bile duct ligation (CBDL). Basal levels of heart rate, mean arterial pressure (MAP), RSNA, and urinary sodium excretion were not affected by intracerebroventricular administration of either losartan or vehicle to CBDL rats. After acute intravenous isotonic saline loading (10% body wt) in vehicle-treated CBDL rats, MAP was unchanged and the decrease in RSNA seen in normal rats did not occur. However, in losartan-treated CBDL rats, there were significant concurrent but transient decreases in MAP (-20 +/- 2 mmHg) and RSNA (-25 +/- 3%). The natriuretic response to acute volume loading in losartan-treated CBDL rats was significantly less than that in vehicle-treated CBDL rats only at those time points where there were significant decreases in MAP. Antagonism of CNS ANG II type 1 receptors augments the renal sympathoinhibitory response to acute volume loading in CBDL. However, the natriuretic response to the acute volume loading is not improved, likely due to the strong antinatriuretic influence of the concomitant marked decrease in MAP (renal perfusion pressure) mediated by widespread sympathetic withdrawal from the systemic vasculature.
Voigt
M D
MD
Departments of Internal Medicine and Physiology, University of Iowa College of Medicine and Veterans Affairs Medical Center, Iowa City, Iowa 52242, USA.
Jones
S Y
SY
DiBona
G F
GF
D000804:Angiotensin II / Q000502:physiology*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003135:Common Bile Duct; D007668:Kidney / Q000294:innervation*; D008026:Ligation; D008106:Liver Cirrhosis, Experimental / Q000503:physiopathology*; D019808:Losartan / Q000494:pharmacology; D008297:Male; D009318:Natriuresis / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D012016:Reference Values; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000503:physiopathology*
D057911:Angiotensin Receptor Antagonists; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D000804:Angiotensin II; D019808:Losartan