A
D/D (deletion/deletion) polymorphism within the ACE (
angiotensin 1-converting
enzyme) gene increases the risk of microalbuminuria, a predictor of atherosclerotic
vascular disease, in
essential hypertension. It is unknown, however, whether this genetic profile is accompanied by disturbed macromolecular permeability of systemic capillary endothelium, possibly in the context of generalized endothelial dysfunction. In the present study, the ACE gene polymorphism was determined by PCR in 79 never-treated uncomplicated hypertensive men and 16 normotensive men as controls. Evaluation variables were TERalb (transcapillary escape rate of
albumin; the 1-h decline rate of intravenous (125)I-
albumin, a measure of integrity of systemic capillary endothelium),
albuminuria and forearm vasodilation to intra-arterial
acetylcholine, an index of NO (
nitric oxide)-mediated vasomotion, in addition to a series of sensitive parameters of
albumin permeation (blood pressure, metabolic status and smoking habits). Analyses were done by comparing
D/D homozygotes with grouped I/D (insertion/deletion) and I/I (insertion/insertion) subjects. TERalb was higher in
D/D hypertensives, who had higher
albuminuria, more frequent microalbuminuria and comparable forearm responsiveness to intra-arterial
acetylcholine. Fasting
glucose and
insulin,
insulin sensitivity, 24-h blood pressure, smoking habits and metabolic parameters did not differ between the two groups. TERalb and urine
albumin values were positively associated in the hypertensive subjects. In conclusion, ACE
D/D homozygosis, independently of several confounding factors, associates with higher TERalb in men with
essential hypertension. This may reflect noxious genetic influences on systemic vascular permeability, a critical control mechanism for
atherogenesis in the absence of grossly impaired NO-mediated arteriolar responsiveness. The parallel behaviour of TERalb and
albuminuria suggests some shared genetically mediated determinant of renal and systemic microvascular abnormalities in
hypertension.