The effects of combined renovascular hypertension and diabetes mellitus on the rat heart were investigated in order to detect possible synergistic effects of the two conditions. Hypertensive diabetic and hypertensive non-diabetic animals were compared to diabetic and non-diabetic controls. Hypertension was established for 12 weeks by a surgical stenosis of the left renal artery; diabetes mellitus was maintained for 8 weeks by a single intraperitoneal injection of 60 mg/kg streptozotocin. Light microscopic stereology did not reveal significant divergences between diabetic hypertensives and non-diabetic hypertensives. Hypertension induced a focal perivascular and interstitial fibrosis with increased volume densities of non-vascular interstitium and fibrosis (P less than 0.001). Capillary density (QA) was decreased in transverse sections (P less than 0.01) and increased in longitudinal sections (P less than 0.01). This indicates a three-dimensional remodelling of the capillary bed with an increased number of obliquely running capillaries. At least the length density (LV) of capillaries (mm/mm3) tends to be normalized in long-term renovascular hypertension. At the ultrastructural level, a synergism of hypertension and diabetes mellitus was observed: the volume ratio of mitochondria to myofibrils was significantly decreased in hypertensive diabetics, but not in non-diabetic hypertensives or in diabetics. This may enhance the risk of cardiac deterioration. We conclude that the primary target of the synergistic damage in hypertensive diabetic heart muscle disease is the myocardial cell and not the cardiac interstitium.
The serum concentration of 7S collagen was measured radioimmunologically as a marker of basement membrane type IV collagen synthesis in diabetic and nondiabetic rats with Goldblatt hypertension. In non-diabetic rats the 7S collagen level was significantly raised after induction of hypertension (51%; p less than 0.001), and showed a positive correlation with relative heart weight as an integral parameter of hypertension (r = 0.63; p less than 0.01). In diabetic rats, which displayed a 7S collagen concentration roughly 2.5 times as high as the metabolically normal animals, the 7S collagen level was 27% higher in the hypertensive animals (p less than 0.01). There was no correlation with blood pressure or heart weight, but only a positive correlation with blood glucose (r = 0.51; p less than 0.05). The results indicate that haemodynamic alterations may alter basement membrane collagen metabolism. However, type IV collagen metabolism in diabetes is influenced to a greater extent by metabolic than by haemodynamic factors.
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