[Effects of chronic losartan treatment on myocardial, vascular structure and reactivity with aging in spontaneously hypertensive rats (SHR): its effects compared with those of captopril].
To compare the effects of an angiotensin II (Ang II)-receptor antagonist and an angiotensin-converting enzyme (ACE) inhibitor on myocardial, vascular structure and reactivity, SHR (5-week-old) were treated with losartan of captoril for 16 weeks. Losartan (10 mg/kg/day, p.o.) and captopril (30 mg/kg/day, p.o.) significantly prevented the development of hypertension with aging, and the effects by these drugs were almost similar. Losartan and captopril significantly reduced the ventricular weight and the thickening of the coronary artery. Maximal coronary flow (MCF) induced by adenosine in the isolated heart was significantly higher in both the losartan and captopril groups. However, MCF in the captopril group was significantly lower than that in the losartan group. The pressor response to exogenous norepinephrine in the mesenteric arterial bed was significantly lower in the losartan group, whereas that in the captopril group was not. These findings suggest that the local Ang II produced by enzymes other than ACE also may play a role in vascular hypertrophy and hyperresponsiveness in SHR.
Nishimura
N
N
New Drug Research Laboratories, Kanebo, Ltd., Osaka, Japan.
Takase
H
H
Morita
T
T
D000375:Aging / Q000473:pathology / Q000502:physiology; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000494:pharmacology; D001161:Arteriosclerosis / Q000517:prevention & control; D001713:Biphenyl Compounds / Q000008:administration & dosage* / Q000494:pharmacology; D002216:Captopril / Q000008:administration & dosage* / Q000494:pharmacology; D003326:Coronary Circulation / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects / Q000473:pathology; D006352:Heart Ventricles / Q000473:pathology; D006973:Hypertension / Q000517:prevention & control; D007093:Imidazoles / Q000008:administration & dosage* / Q000494:pharmacology; D066298:In Vitro Techniques; D019808:Losartan; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011918:Rats, Inbred SHR; D013777:Tetrazoles / Q000008:administration & dosage* / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects
D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D007093:Imidazoles; D013777:Tetrazoles; D002216:Captopril; D019808:Losartan