Dysregulation of angiotensin II synthesis is associated with salt sensitivity in the spontaneous hypertensive rat.
(1) Salt sensitive hypertension, which occurs as a result of treatment with nitric oxide synthase inhibitors, is associated with a loss of the usual down-regulatory effect of dietary sodium on angiotensin II (Ang II) synthesis. In the spontaneous hypertensive rat (SHR), which suffers a relative NO deficiency, the hypertension is in part salt sensitive. We sought to determine therefore whether the salt sensitive component to the hypertension was associated with a loss of the regulatory effect of dietary sodium on Ang II synthesis. (2) Male SHR were placed on low, intermediate or high salt diets for 4 weeks and their blood pressure recorded. After 4 weeks, blood was collected for determination of renin, angiotensinogen, Ang I, Ang II and aldosterone concentrations, as well as ACE activity. (3) The increase in systolic blood pressure in rats on the high salt diet was significantly greater than in those on the low (P < 0.005) and intermediate salt diets (P < 0.0005). Plasma renin and aldosterone concentrations and ACE activity decreased with increasing dietary sodium. However, the concentrations of Ang II and angiotensinogen both increased in the rats on the high salt diet (Ang II: P < 0.05; angiotensinogen: P < 0.05). (4) We conclude that the hypertension in the SHR is in part salt sensitive and that this salt sensitive component is associated with a loss of the normal down-regulatory effect of dietary sodium on Ang II and angiotensinogen synthesis.
Hodge
G
G
Hypertension Service, South-Western Sydney Clinical School, University of New South Wales, Bankstown, NSW, Australia.
Ye
V Z C
VZ
Duggan
K A
KA
D000450:Aldosterone / Q000097:blood; D000803:Angiotensin I / Q000097:blood; D000804:Angiotensin II / Q000096:biosynthesis* / Q000097:blood; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000808:Angiotensinogen / Q000097:blood; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D006973:Hypertension / Q000201:enzymology / Q000503:physiopathology*; D019808:Losartan / Q000494:pharmacology; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000097:blood / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011945:Receptors, Angiotensin / Q000378:metabolism; D012083:Renin / Q000097:blood; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage / Q000494:pharmacology*
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D011945:Receptors, Angiotensin; D017673:Sodium Chloride, Dietary; D000808:Angiotensinogen; D000804:Angiotensin II; D000450:Aldosterone; D000803:Angiotensin I; D007703:Peptidyl-Dipeptidase A; D012083:Renin; D019808:Losartan