Angiotensin II, sodium, and cardiovascular hypertrophy in spontaneously hypertensive rats.
Angiotensin II (Ang II) may cause cardiovascular hypertrophy as a consequence of increased blood pressure or possibly by direct trophic actions. To dissociate Ang II and blood pressure in young spontaneously hypertensive rats (SHR), we used sodium loading during angiotensin converting enzyme inhibitor treatment. Animals were treated between 6 and 10 weeks of age with perindopril to lower Ang II and blood pressure, or with perindopril and 1% saline drinking fluid or perindopril and aldosterone infusion to lower Ang II but maintain high blood pressure. Blood pressure, heart weight, and media/lumen ratio of mesenteric resistance arteries were studied while rats were on treatment at 10 weeks of age and 15 weeks after treatment at 25 weeks of age. Perindopril lowered blood pressure and inhibited the development of cardiovascular hypertrophy. Saline or aldosterone restored high blood pressure during perindopril treatment and resulted in increased heart weight/body weight and resistance artery media/lumen ratios in direct proportion to the elevation of blood pressure. Because increased structure occurred despite perindopril treatment, we conclude that direct trophic actions of Ang II are not essential for the development of cardiovascular hypertrophy in young SHR and that the antitrophic actions of angiotensin converting enzyme inhibitors depend more on changes in blood pressure than on Ang II. However, restoration of blood pressure and structure by sodium during perindopril treatment raises the possibility that the design of the cardiovascular system and blood pressure may depend indirectly on Ang II through effects on sodium metabolism.
Harrap
S B
SB
University of Melbourne, Department of Medicine, Austin Hospital, Heidelberg, Victoria, Australia.
Mitchell
G A
GA
Casley
D J
DJ
Mirakian
C
C
Doyle
A E
AE
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D006332:Cardiomegaly / Q000209:etiology* / Q000503:physiopathology; D006973:Hypertension / Q000503:physiopathology*; D007211:Indoles / Q000494:pharmacology; D008297:Male; D020913:Perindopril; D051381:Rats; D011918:Rats, Inbred SHR; D012964:Sodium / Q000494:pharmacology*
D007211:Indoles; D000804:Angiotensin II; D012964:Sodium; D020913:Perindopril