Effects of amlodipine on nitric oxide synthase mRNA expression and coronary microcirculation in prolonged nitric oxide blockade-induced hypertensive rats.
We evaluated the effects of long-term treatment with amlodipine, a calcium antagonist, on nitric oxide synthase (NOS) activity and NOS messenger RNA (mRNA) expression in the left ventricle (LV) and its relation to coronary reserve, and microvascular remodeling in Nomega-nitro-L-arginine methyl ester (L-NAME)-induced hypertensive rats. Seventeen male Sprague-Dawley rats were given L-NAME (60 mg/kg/day) in drinking water for 6 weeks to induce hypertension, and then treated with amlodipine (L-NAME + A, 5 mg/kg/day, n = 9), or a vehicle (L-NAME + V, n = 8) for 4 weeks. Age-matched rats (C, n = 8) served as the control group. An increased blood pressure in L-NAME + V was significantly decreased in L-NAME + A. Nitrite production and endothelial cell (e) NOS mRNA in the LV were significantly decreased in L-NAME + V compared with C, and were significantly increased in L-NAME + A compared with C and L-NAME + V. L-NAME + V had a significantly decreased coronary reserve and capillary density, and a significantly increased type I collagen mRNA expression, wall-to-lumen ratio, perivascular fibrosis, myocardial fibrosis, and myocyte cross-sectional area. These parameters in the microvasculature were significantly improved by amlodipine. We concluded that NOS activity and eNOS mRNA were significantly increased by amlodipine in the LV of L-NAME-induced hypertensive rats, and that these increase NOS activity and eNOS mRNA expression may play a role in the amelioration of coronary reserve and microvascular remodeling.
Kobayashi
N
N
Department of Medicine, Dokkyo University School of Medicine, Mibu, Tochigi, Japan.
Yanaka
H
H
Tojo
A
A
Kobayashi
K
K
Matsuoka
H
H
D017311:Amlodipine / Q000494:pharmacology*; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects; D006973:Hypertension / Q000503:physiopathology*; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000235:genetics*; D052250:Nitric Oxide Synthase Type III; D012333:RNA, Messenger / Q000032:analysis*; D051381:Rats; D017207:Rats, Sprague-Dawley
D002121:Calcium Channel Blockers; D012333:RNA, Messenger; D017311:Amlodipine; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D019331:NG-Nitroarginine Methyl Ester