The study is intended to explore various factors which contribute to hypertensive vascular damage in the rat and to investigate the mechanisms involved. It is divided into two parts. The first part compares damage to the aorta as judged by endothelial replication, permeability studies, and high resolution microscopy in models with high and low renin content of the blood. The effects of prolonged exposure of small arteries to renin on the responses to hypertension will be studied, and the severity and extent of arterial and arteriolar necrosis in a renin-dependent model compared with those in animals with non renin-dependent hypertension. Glomerular changes will be analyzed and compared in these two models, and a new model of hypertension will be developed to further extend these comparisons. The second part seeks to explain whether heparin attenuates the acute necrotizing changes seen in experimental hypertension by its anticoagulant action or by interference with the permeability of the vessel wall. The studies should determine first, whether renin-angiotensin is damaging to large and small blood vessels, and second whether heparin can interfere with arterial permeability and if so whether it acts by its effect on charge on the endothelium.
