Angiotensinogen dependency of blood pressure in two high-renin hypertensive rat models.
In this analysis we investigated whether angiotensinogen (Aogn) levels were related to blood pressure (BP) in two hypertensive rat models when renin secretion was either under physiologic regulation or out of control. These relationships were investigated using BP data from previous reports in which SHRsp and Dahl S rats were studied for 10 to 12 weeks while ingesting a high-salt diet with and without the angiotensin II (AngII) antagonist losartan. During the first 4 weeks of high-salt diet, plasma renin concentration (PRC) was appropriately suppressed but it subsequently increased paradoxically in both strains. During the first 4 weeks, when renin secretion was under normal control, as indicated by its suppression by the high-salt diet and by an inverse relationship between PRC and BP (r = -0.69, P < .001 and r = -0.53, P < .01 in Dahl S and SHRsp, respectively), there was no relationship between BP and plasma Aogn. In contrast, when renin secretion increased paradoxically, the inverse relationship between BP and PRC was lost and a positive relationship was found between BP and plasma Aogn in both Dahl S rats (r = 0.70, P < .01) and SHRsp (r = 0.57, P < .01). There was no relationship between BP and Aogn in either strain during treatment with losartan either before or after 4 to 6 weeks of salt feeding. These results show Aogn dependency of BP, but only under conditions in which renin cannot feed back normally. The Aogn relationship to BP was most likely dependent on the vasoconstrictor effect of AngII since it was lost during AngII AT1 receptor antagonism.
Gahnem
F
F
Department of Medicine, Cornell University Medical College, New York, New York 10021.
von Lutterotti
N
N
Camargo
M J
MJ
Laragh
J H
JH
Sealey
J E
JE
D000804:Angiotensin II / Q000037:antagonists & inhibitors; D000808:Angiotensinogen / Q000097:blood*; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D007093:Imidazoles / Q000494:pharmacology; D019808:Losartan; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D011919:Rats, Inbred Strains; D012083:Renin / Q000097:blood*; D012982:Sodium, Dietary; D013777:Tetrazoles / Q000494:pharmacology
D001713:Biphenyl Compounds; D007093:Imidazoles; D012982:Sodium, Dietary; D013777:Tetrazoles; D000808:Angiotensinogen; D000804:Angiotensin II; D012083:Renin; D019808:Losartan