The role of activated vascular angiotensin II generation in vascular hypertrophy in one-kidney, one clip hypertensive rats.
OBJECTIVE
To investigate the role of vascular angiotensin II (Ang II) in the vascular thickening of one-kidney, one clip (1-K, 1C) hypertensive rats, which show normal plasma renin activity.


METHODS
The type 1 Ang II receptor antagonist TCV-116 (1 mg/kg per day), the angiotensin converting enzyme (ACE) inhibitor delapril (20 mg/kg per day), hydralazine (20 mg/kg per day) or vehicle were administered to four groups of 1-K, 1C rats aged 6-10 weeks. Vehicle was also given to uninephrectomized rats.


RESULTS
The aortae of 1-K, 1C rats contained significantly higher levels of Ang II than those of uninephrectomized rats and showed hypertrophy, but not hyperplasia of their medial smooth muscle cells. Hypertrophy was estimated by immunohistochemical staining of alpha-actin. Hyperplasia was estimated by DNA content and incorporation of 5-bromo-2'-deoxyuridine. The blood pressure of the 1-K, 1C rats was not affected by either TCV-116 or delapril, even at doses sufficient to induce depressor effects in spontaneously hypertensive rats. However, subdepressor doses of TCV-116 and delapril both significantly reduced the alpha-actin-stained area to 78 and 73%, respectively, of that in the 1-K, 1C rats, whereas a depressor dose of hydralazine did not affect the alpha-actin-stained area. The level of Ang II in the aorta, but not in plasma, was suppressed by delapril but not by hydralazine.


CONCLUSIONS
These results suggest strongly that vascular Ang II plays a major role in the development of vascular hypertrophy, independently of plasma Ang II, bradykinin and ACE-independent pathways of Ang II generation, and in the regulation of blood pressure in this normoreninaemic hypertensive model.
Yu
H
H
Department of Geriatric Medicine, Osaka University Medical School, Suita, Japan.
Rakugi
H
H
Higaki
J
J
Morishita
R
R
Mikami
H
H
Ogihara
T
T
D000199:Actins / Q000378:metabolism; D000804:Angiotensin II / Q000502:physiology*; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D001562:Benzimidazoles / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D004247:DNA / Q000378:metabolism; D006830:Hydralazine / Q000494:pharmacology; D006978:Hypertension, Renovascular / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology*; D006984:Hypertrophy; D007189:Indans / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D013777:Tetrazoles
D000199:Actins; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D007189:Indans; D013777:Tetrazoles; D000804:Angiotensin II; D006830:Hydralazine; D004247:DNA; C077793:candesartan cilexetil; C047759:delapril