ACE gene insertion/deletion polymorphism and capillary permeability in hypertension

Giulia Dell'Omo , Giuseppe Penno , Laura Pucci , Daniela Lucchesi , Carmen Fotino , Stefano del Prato , Roberto Pedrinelli , Roberto Pedrinelli (1)

1 Dipartimento Cardio Toracico

RATIONALE: A D/D polymorphism within the ACE gene increases the risk of microalbuminuria, a predictor of atherosclerotic vascular disease, in essential hypertension. It is unknown, however, whether that genetic profile is accompanied by disturbed macromolecular permeability of systemic capillary endothelium, possibly in the context of a generalized endothelial dysfunction. METHODS: The ACE gene polymorphism was determined by polymerase chain reaction in 79 never treated, uncomplicated hypertensive and 16 normotensive men as controls. Evaluation variables were the transcapillary escape rate of albumin (TERalb, the 1-hour decline rate of intravenous 125}I-albumin, a measure of integrity of systemic capillary endothelium), albuminuria, forearm vasodilation to intra-arterial acetylcholine, an index of nitric oxide-mediated vasomotion, in addition to a series of sensitive parameters for albumin permeation (BP, metabolic status, smoking habits). RESULTS: Analyses were done by comparing D/D homozygotes vs grouped I/D and I/I subjects. TER Alb} was higher in D/D hypertensives characterized also by higher albuminuria, more frequent microalbuminuria and comparable forearm responsiveness to intra-arterial acetylcholine. 24-hr BP, fasting glucose and insulin, insulin sensitivity, smoking habits, metabolic parameters did not differ. TERalb and urine albumin values were positively associated. CONCLUSIONS: ACE D/D homozygosis associates with higher TERalb independent of several confounding factors in essential hypertensive men. That behavior may reflect noxious genetic influences on systemic vascular permeability, a critical control mechanism for atherogenesis in absence of grossly impaired nitric-oxide mediated arteriolar responsiveness. The parallel behavior of TERalb and albuminuria suggests some shared genetically mediated determinant of renal and systemic microvascular abnormalities in hypertension.

Mots clés: Medicine

Giulia Dell'Omo, Giuseppe Penno, Laura Pucci, Daniela Lucchesi, Carmen Fotino, et al.. ACE gene insertion/deletion polymorphism and capillary permeability in hypertension. Clinical Science, 2006, 111 (6), pp.357-364. ⟨10.1042/CS20060165⟩. ⟨hal-00479331⟩