Whole Body and Regional Hemodynamic Effects of Minoxidil in the Conscious Dog

Humphrey, Stephen J.; Zins, Gerald R.

doi:10.1097/00005344-198406060-00001

Cited by 40 publications

(16 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Direct evidence for an effect on vascular wall tension is not available in the dog, although significant increases in coronary blood flow is a characteristic feature of the pharmacology of vasodilators inducing coronary arteriopathy. This is the case for minoxidil (7), hydralazine (3), dopamine (11), and the PDE III inhibitors SK&F 94836 and CI 914 (5,19). Although the arteriopathy following vasodilator administration may be related to the prolonged hemodynamic effects of these compounds, the exact relationships have as yet not been established and await further investigation.…”

Section: Discussionmentioning

confidence: 99%

Characterization of Coronary Arterial Lesions in the Dog Following Administration of SK&F 95654, a Phosphodiesterase III Inhibitor

1996

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

Characterization of Coronary Arterial Lesions in the Dog Following Administration of SK&F 95654, a Phosphodiesterase III Inhibitor

1996

View full text Add to dashboard Cite

“…terminations. Whole body hemodynamics and blood flow to the various chambers of the heart and other selected tissues were measured using the radiolabeled microsphere technique (15). All measurements were made in conscious dogs 3 to 4 hr after single oral doses of minoxidil.…”

Section: Materials and 'Methodsmentioning

confidence: 99%

“…This is indeed the case with minoxidil. Coronary blood flow was increased acutely by 6-to lOefold in all chambers of the heart as compared with fractionally smaller Increases in blood flow to the other parts of the body (15). Formation of arterial medial injury and loss of capillary integrity (hemorrhage) may have the same pharmacologic basis but a different mechanism.…”

Section: Mechanism Ofright Atrial Lesions In Dogs Treated With Toxic mentioning

confidence: 96%

Pathogenesis of Cardiovascular Alterations in Dogs Treated with Minoxidil

et al. 1989

Self Cite

View full text Add to dashboard Cite

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.

show abstract

“…It has been postulated that these lesions are the result of disturbances in critical wall tension due to vasodilator-related relaxation of the medial smooth muscle (23,33,34). Direct evidence of an effect on vascular wall tension is not available for many of the vasodilators reported to induce vascular lesions, but increased coronary blood flow has been demonstrated for minoxidil (21,33), hydralazine (9), endothelin receptor antagonist (32), and PDE III inhibitor SK&F 94836 (15).…”

Section: Vasoactive Induced Arterial Lesions In the Dogmentioning

confidence: 99%

Differentiating Spontaneous from Drug-Induced Vascular Injury in the Dog

et al. 2003

View full text Add to dashboard Cite

When vascular injury is observed in dogs used in preclinical toxicology studies, careful evaluation of the lesions is warranted, especially when differentiating drug-induced vascular changes from spontaneous findings, such as idiopathic canine polyarteritis. The clinical signs as well as the nature and distribution of lesions can often be distinguishing, as is the case with vasoactive drugs, including vasodilators and/or positive inotropes (hydralazine, minoxidil, endothelin receptor antagonists, and phosphodiesterase III inhibitors). For most types of vasodilator-induced vascular injury, the lesion is often restricted to coronary arteries, whereas in idiopathic canine polyarteritis, arterial lesions not only involve coronary arteries, but also medium to small arteries of other organs. In addition, the nature of the changes in vessels yields important clues. Medial and adventitial hemorrhage is generally associated with vasodilator-induced arterial lesion, whereas hemorrhage is generally absent in idiopathic polyarteritis. Although idiopathic canine polyarteritis can generally be differentiated from vasoactive-induced vascular injury in dogs, there are increasing incidences of this type of polyarteritis in dogs receiving any 1 of a number of unrelated classes of compounds, suggestive of an exacerbation of the spontaneous disease. Therefore, in order to differentiate drug-induced injury from idiopathic canine polyarteritis, it is critical that examination of the vascular pathology be conducted with good understanding of clinical, pharmacological, and mechanistic data associated with the drug.

show abstract

Whole Body and Regional Hemodynamic Effects of Minoxidil in the Conscious Dog

Cited by 40 publications

References 0 publications

Characterization of Coronary Arterial Lesions in the Dog Following Administration of SK&F 95654, a Phosphodiesterase III Inhibitor

Characterization of Coronary Arterial Lesions in the Dog Following Administration of SK&F 95654, a Phosphodiesterase III Inhibitor

Pathogenesis of Cardiovascular Alterations in Dogs Treated with Minoxidil

Differentiating Spontaneous from Drug-Induced Vascular Injury in the Dog

Contact Info

Product

Resources

About