Cardiovascular pharmacology of nicardipine in animals.

Takenaka, Toichi; Asano, Masaharu; Shiono, Kumiko; Shibasaki, Masayuki; Inagaki, Osamu

doi:10.1111/j.1365-2125.1985.tb05140.x

Cited by 56 publications

(24 citation statements)

References 28 publications

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“…It was also not known why some vasodilators that cause coronary vascular injury were associated with right atrial lesions (7,10,21), and others were not (11,22,28,38). Right atrial hemorrhage in dogs acutely treated with hydralazine (22) was not seen in chronically treated dogs (Diener, personal communication) probably because of tolerance that develops to the pharmacologic effects of hydralazine within 4 d (37).…”

Section: Mechanism Ofright Atrial Lesions In Dogs Treated With Toxicmentioning

confidence: 99%

Pathogenesis of Cardiovascular Alterations in Dogs Treated with Minoxidil

et al. 1989

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Minoxidil and other potent vasodilators cause coronary arterial injury, right atrial hemorrhagic lesions, and subendocardial necrosis in dogs, This paper discusses the pathogenesis of coronary arterial and right atrial lesions associated with minoxidil in the dog, Acute coronary vascular injury characterized by segmental medial hemorrhage and necrosis and perivascular inflammation occurred only during the first few days of treatment, after which tolerance to further acute injury developed, At 30 d or more of treatment, coronary vascular injury was characterized by perivascular fibrosis rarely attended by medial distortion or hyperplasia and subintimal thickening, changes consistent with responses to previous injury, Right atrial hemorrhagic lesions, unlike coronary vascular injury, often became progressively more extensive with continued treatment. At 3 d, atrial hemorrhage and inflammation were confined to the subepicardium ofthe right atrium, evidently around affected subepicardial branches of the right coronary artery, At 30 d, fibrovascular proliferative right atrial lesions (granulation tissue with evidence of continual hemorrhage) extended from the epicardium to the myocardium, with eventual replacement ofthe atrial wall by mature connective tissue at I yr of treatment. Minoxidil-induced cardiovascular lesions were not prevented by treatment with a l3-blocker (propranolol), or an a-blocker (dibenzylene), or by sympathetic neural activity suppression (surgical sympathectomy or constant carotid sinus nerve stimulation), suggesting that the sympathetic response to the pharmacologic activity of minoxidil was not responsible for the induction of the cardiovascular lesions. Minoxidil-related vascular lesions were confined to the most pharmacologically responsive segment of the arterial system, the coronary arteries, suggesting that medial injury may have been associated with tensile changes in the arterial wall.

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Section: Mechanism Ofright Atrial Lesions In Dogs Treated With Toxicmentioning

confidence: 99%

Pathogenesis of Cardiovascular Alterations in Dogs Treated with Minoxidil

et al. 1989

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“…Significant hypotensive effects were observed after long-term oral administration of nicardipine in SHR (24). A long-term nifedipine-treatment has also been shown to normalize blood pressure concomitantly with a reduction of myocardial hypertrophy: left ventricular pumping function was improved and coronary reserve enhanced (23).…”

Section: Discussionmentioning

confidence: 92%

Influence of spontaneous hypertension and cardiac hypertrophy on the severity of ischemic arrhythmias in the rat

1988

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Cardiac hypertrophy (CH) and hypertension (HT) are major determinants of sudden cardiac death in patients with coronary artery disease. To investigate the hypothesis that CH and HT increase the incidence of severe ventricular arrhythmias in an animal model, we performed a 30-min period of coronary artery ligation in anesthetized spontaneously hypertensive rats (SHR), normotensive Wistar Kyoto (WKY) and Wistar (W) rats. The incidence and duration of ventricular fibrillation resulting from coronary artery occlusion were significantly (p less than 0.01) increased in hypertensive rats compared to normotensive animals. The calcium entry blocker nicardipine was administered orally to SHR either chronically for 8 weeks (20 mg.kg-1 twice daily) or acutely as a single dose of 20 mg.kg-1. After long-term treatment with nicardipine, left ventricular hypertrophy index and systolic blood pressure were significantly (p less than 0.001) reduced when compared to vehicle-treated SHR, whereas a single administration of nicardipine only decreased blood pressure without affecting cardiac mass. In the long-term nicardipine-treated SHR group, acute coronary artery ligation induced significantly less ventricular fibrillation (p less than 0.05) and mortality (p less than 0.001) than in acutely nicardipine-treated or untreated SHR groups. In conclusion, the data suggest that the severity and incidence of lethal ventricular arrhythmias are more elevated in hypertensive than in normotensive rats and this may be related to the myocardial hypertrophic state.

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“…Coronary vascular lesions in dogs treated with hydralazine were not seen in previous studies (Diener, personal communication), probably because of differences in study design and/or doses used. Minoxidil-related acute coronary vascular injury was not detected in the initial preclinical studies where dogs were killed after 30 days of treatment (5, 22). Like papillary necrosis (2,3, 16), vascular injury apparently occurs only during the first few days of treatment with vasodilators (3, 10, 16).…”

Section: Discussionmentioning

confidence: 99%

“…Coronary vascular injury and persistent hemorrhage into the right atrium, discovered in dogs treated with minoxidil (5, 12,22), have recently been noted in dogs treated with other vasodilators such as theobromine (8) and nicorandil (Mesfin, unpublished). Coronary vascular injury with these and other vasodilator/cardioactive drugs including.SK&F 94 120 (10) and CI-930 (Gough, personal communication), like papillary necrosis (2,3), apparently occurs only during the initial few days of treatment.…”

Section: Introductionmentioning

confidence: 99%

Cardiovascular Alterations in Dogs Treated with Hydralazine

1987

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Groups of 5 male beagle dogs were treated orally with hydralazine tablets in gelatin capsules at a dose of 12 or 24 mdkg twice a day (6 hours apart) for 2 consecutive days. Five male dogs treated with empty gelatin capsules served as untreated controls. Clinical findings and heart rate changes during treatment and terminal body weight, hematology, and blood chemistry changes were evaluated. The heart, liver, kidneys, spleen, and thymus of each animal were examined microscopically. Dogs in the 12 mdkg group ate less than control group. Dogs treated with 24 mdkg did not eat and vomited. Heart rates in both ofthe treated groups increased by 60 to 80% within 2 hours of treatment and remained high during the entire treatment period. Significant ' hematologic change was confined to a slight increase in platelet number of dogs treated with 24 mg/kg. Serum glucose was increased in the hydralazine treated dogs. Conjugated serum bilirubin was increased and serum potassium, chloride and phosphorus were decreased in the 24 mg/kg group. Blood urea nitrogen and serum chloride were slightly increased in dogs treated with 12 mglkg. Treatment-related pathologic alterations were confined to the heart. Two dogs from each of the hydralazine groups experienced acute localized hemorrhage into the epicardium and subepicardium of the right atrium. The media of the muscular branches of the coronary arteries, especially the left coronary artery, was hemorrhagic in 3 dogs from the 24 mg/kg group.Medial necrosis, when seen, tended to be proportional to the severity of medial hemorrhages. There was no necrosis in the papillary muscles of the heart. These acute cardiovascular alterations in dogs treated with hydralazine for 2 days-believed to be related to exaggerated pharmacologic effects of the drug-were similar to the lesions seen in dogs treated with minoxidil for 2 to 3 days.

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Cardiovascular pharmacology of nicardipine in animals.

Cited by 56 publications

References 28 publications

Pathogenesis of Cardiovascular Alterations in Dogs Treated with Minoxidil

Pathogenesis of Cardiovascular Alterations in Dogs Treated with Minoxidil

Influence of spontaneous hypertension and cardiac hypertrophy on the severity of ischemic arrhythmias in the rat

Cardiovascular Alterations in Dogs Treated with Hydralazine

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