ACE gene insertion/deletion polymorphism modulates capillary permeability in hypertension.
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.
Dell'omo
Giulia
G
Dipartimento Cardio Toracico, Università di Pisa, Pisa, Italy.
Penno
Giuseppe
G
Pucci
Laura
L
Lucchesi
Daniela
D
Fotino
Carmen
C
Del Prato
Stefano
S
Pedrinelli
Roberto
R
D000419:Albuminuria / Q000235:genetics / Q000503:physiopathology; D002199:Capillary Permeability / Q000502:physiology*; D016022:Case-Control Studies; D004251:DNA Transposable Elements / Q000235:genetics*; D004730:Endothelium, Vascular / Q000502:physiology; D005542:Forearm / Q000098:blood supply; D017353:Gene Deletion; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000235:genetics* / Q000503:physiopathology; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D014664:Vasodilation / Q000235:genetics
D004251:DNA Transposable Elements; C488034:ACE protein, human; D007703:Peptidyl-Dipeptidase A