Effects of temocapril and olmesartan on myocardial sympathetic nervous activity and fatty acid metabolism in rats with chronic beta-adrenergic stimulation.
We investigated the effects of an angiotensin-converting enzyme inhibitor (temocapril) and an angiotensin II type 1 receptor blocker (olmesartan) on changes in myocardial sympathetic nervous activity, fatty acid metabolism and myocardial blood flow using 131I-meta-iodobenzylguanidine, 125I-beta-methyl-iodophenyl pentadecanoic acid and 99mTc-tetrofosmin, respectively, in rats with isoproterenol-induced cardiac hypertrophy. Male Sprague-Dawley rats underwent isoproterenol administration (3 mg/kg per day) for 1 week by osmotic mini-pump. The hearts were excised and analyzed for the uptake of meta-iodobenzylguanidine. Beta-methyl-iodophenyl pentadecanoic acid and tetrofosmin in 11 segments in four groups; sham group (saline), isoproterenol group (isoproterenol alone), angiotensin-converting enzyme inhibitor group (isoproterenol and temocapril), and angiotensin II type 1 receptor blocker group (isoproterenol and olmesartan). Isoproterenol significantly increased the heart weight compared with the sham group, whereas it was significantly blunted in the angiotensin-converting enzyme inhibitor and angiotensin II type 1 receptor blocker groups. The ratio of the percent kilogram dose per gram of meta-iodobenzylguanidine to tetrofosmin, an index of myocardial sympathetic nervous activity, was significantly decreased in the isoproterenol group (0.18 +/- 0.01) compared with the sham group (0.41 +/- 0.03). Importantly, these changes were significantly improved in the angiotensin-converting enzyme inhibitor (0.28 +/- 0.01) and the angiotensin II type 1 receptor blocker groups (0.32 +/- 0.01). The ratio of the percent kilogram dose per gram of beta-methyl-iodophenyl pentadecanoic acid to tetrofosmin, an index of myocardial fatty acid metabolism, was significantly decreased in the isoproterenol group (1.30 +/- 0.03) compared with the sham group (1.60 +/- 0.10). In contrast, there were no significant differences in beta-methyl-iodophenyl pentadecanoic acid to tetrofosmin ratios between the sham and angiotensin-converting enzyme inhibitor groups, or the angiotensin II type 1 receptor blocker group. Cardiac hypertrophy induced by chronic beta-adrenergic stimulation is accompanied by impairment of sympathetic nervous activity and fatty acid metabolism. These abnormalities are effectively prevented by the angiotensin-converting enzyme inhibitor and the angiotensin II type 1 receptor blocker.
Ido
Akira
A
First Department of Internal Medicine, Asahikawa Medical College, Asahikawa, Japan.
Hasebe
Naoyuki
N
Takeuchi
Toshiharu
T
Kikuchi
Kenjiro
K
D000320:Adrenergic Fibers / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D006332:Cardiomegaly / Q000139:chemically induced / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism*; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D000068557:Olmesartan Medoxomil; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D013777:Tetrazoles / Q000494:pharmacology*; D013841:Thiazepines / Q000494:pharmacology*
D005227:Fatty Acids; D007093:Imidazoles; D011943:Receptors, Adrenergic, beta; D013777:Tetrazoles; D013841:Thiazepines; D000068557:Olmesartan Medoxomil; C055603:temocapril hydrochloride