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.

Relative renal ischemia, produced by a variety of interventions, is modulated or buffered by prostaglandins synthesized within the kidney. These prostaglandins, however, do not account for renal autoregulation in its classic sense. They can facilitate salt and water excretion, largely through effects on physical forces in proximal peritubular capillaries, as evidenced by augmented renal blood flow. Renal prostaglandins may play a role in chronic water balance, but they probably are not important in chronic electrolyte homeostasis. There are several potential mechanisms by which renal prostaglandins could exert antihypertensive efects. Establishment of the importance of these agents, however, as antihypertensive hormones remains a challenge for future investigation.

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