Effects of chronic treatment with carvedilol on abnormalities of endothelium-dependent relaxation and structure of endothelium in resistance arteries of SHRSP.
1. This study investigated the effects of chronic treatment with carvedilol, a beta-blocking agent with an alpha-blocking activity, on blood pressure, endothelium-dependent relaxation and the endothelial structure of the mesenteric resistance artery in stroke-prone spontaneously hypertensive rats (SHRSP). 2. Chronic treatment with carvedilol at a dose range of 30-120 mg/kg per day lowered systolic blood pressure of SHRSP from 234.9 +/- 3.3 to 198.7 +/- 3.1 mmHg at 16 weeks of age. 3. Acetylcholine-induced endothelium-dependent relaxation was impaired in the mesenteric artery from SHRSP and high concentrations of acetylcholine produced contractions. The impairment of the relaxation was abolished in the presence of indomethacin. Carvedilol treatment improved the impairment in the preparation from SHRSP. The structural abnormality of endothelium was observed in the preparation from SHRSP. The abnormality could be prevented by the antihypertensive treatment. 4. These results suggest that the impairment of endothelium-dependent relaxation in the preparation from SHRSP is due to the corelease of an endothelium-derived contracting factor which is considered to be a product of cyclo-oxygenase pathway of arachidonic acid cascade and that the impairment can be prevented by the antihypertensive treatment with carvedilol.
Sasaki
F
F
Faculty of Pharmaceutical Sciences, Kinki University, Higashi-Osaka, Japan.
Yamamoto
K
K
Shimamura
K
K
Shibutani
T
T
Hashimoto
H
H
Tanaka
M
M
Sunano
S
S
D000109:Acetylcholine / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002227:Carbazoles / Q000494:pharmacology*; D000077261:Carvedilol; D002561:Cerebrovascular Disorders / Q000235:genetics / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology*; D008854:Microscopy, Electron; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D011412:Propanolamines / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol; D000109:Acetylcholine