Predisease biological markers: early diagnosis and prevention of arterial hypertension

This review examines 2 potentially important morbid changes that may precede the onset of hypertension—capillary rarefaction (CR) and large artery rigidity (LAR). The mechanisms responsible for CR, currently measured in the skin microcirculation, as well those responsible for LAR, have yet to be fully delineated. Nor has the duration been determined of the latent period between the occurrence of these lesions and the onset of blood pressure elevation. It has been known for 2 decades that, because of the kidney's relatively rigid capsule, alterations in the abundant postglomerular microcirculation network (which can accommodate circa 80% of total renal blood flow) can lead to endothelial plasma leakage. Even a small amount of plasma leakage can increase interstitial pressure and lead to capillary collapse and CR. Simultaneously, or at a later time, these alterations could have an impact on the reflection wave profile in the thoracic aorta and, via abnormal endothelial proliferation and other vascular effects, give rise to LAR. Nonpharmacologic and/or pharmacologic interventions have been shown to exert positive effects on CR and/or LAR. Recent studies have demonstrated the beneficial actions of a bradykinin B2-receptor antagonist (HOE140) in the spontaneously hypertensive rat, the classic rat model for essential hypertension. The fact that CR and LAR both precede blood pressure elevation could serve as a basis for designing strategies to prevent hypertension from occurring. Because modern tools capable of measuring CR and LAR noninvasively have been developed, it should soon be feasible to identify these 2 prehypertension markers in individual patients.