Significant target organs for hypertension and cardiac hypertrophy by angiotensin-converting enzyme inhibitors.
To clarify the mechanisms by which angiotensin-converting enzyme (ACE) inhibitors lower blood pressure or inhibit cardiac hypertrophy, we analyzed the correlations among tissue ACE activities, blood pressure and cardiac hypertrophy. In spontaneously hypertensive rats (SHR), blood pressure, heart weight and ACE activities in plasma and various tissues were measured 3, 24 and 48 h after repeated daily treatment for 2 weeks with the ACE inhibitors trandolapril, perindopril, temocapril and enalapril. For all four ACE inhibitors, blood pressure and ACE activities in the plasma, aorta and kidney were significantly reduced 3 h after the last treatment. Although hypotensive effects were maintained at 24 h, ACE activities in plasma were not suppressed by temocapril and enalapril. Even at 3 h, enalapril could not suppress ACE activity in the brain, and temocapril and enalapril could not inhibit ACE activities in the heart. Significant correlations between ACE activity in the aorta and blood pressure were observed for all four ACE inhibitors, while the ACE activities in the heart and brain were not correlated with changes in blood pressure. Significant decreases in the ratio of heart weight to body weight were observed in SHR treated with trandolapril and perindopril, whereas they were not observed with temocapril and enalapril. The ratio of heart weight to body weight was significantly correlated with ACE activity in the heart. ACE activities in vascular tissues and the heart may be important targets in terms of the ability of ACE inhibitors to lower blood pressure or inhibit cardiac hypertrophy, respectively.
Takai
Shinji
S
Department of Pharmacology, Osaka Medical College, Takatsuki 569-8686, Japan. Pha010@art.osaka-med.ac.jp
Jin
Denan
D
Sakaguchi
Masato
M
Miyazaki
Mizuo
M
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000201:enzymology; D006332:Cardiomegaly / Q000517:prevention & control*; D006973:Hypertension / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology; D007668:Kidney / Q000201:enzymology; D008297:Male; D009206:Myocardium / Q000201:enzymology / Q000473:pathology; D009929:Organ Size; D007703:Peptidyl-Dipeptidase A / Q000097:blood / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D013997:Time Factors
D000806:Angiotensin-Converting Enzyme Inhibitors; D007703:Peptidyl-Dipeptidase A